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HI³ Members on the Anschutz Medical Campus


​The HI3 has welcomed the participation of all immunology and immunotherapy-related basic and/or clinical and translational investigators at all levels of training and expertise on the greater Anschutz Medical Campus as members.

If interested in becoming a member of the HI3, please email the Assistant Director, Aimee Bernard (Aimee.Bernard@ucdenver.edu) your request with a short description of your research interests. Thank you!

 ALLERGY & IMMUNOLOGY

F. Dan Atkins, MD
Dr. Atkins is the Section Head for Allergy and the Co-Director of the Gastrointestinal Eosinophilic Disease Program at Children's Hospital Colorado. Dan’s research interests include better understanding the immunologic mechanisms of different forms of food allergy and eosinophilic gastrointestinal disorders.

Cullen Dutmer, MD
Dr. Dutmer is an Assistant Professor in the Department of Pediatrics, Division of Allergy & Immunology at Children’s Hospital Colorado.  Cullen’s clinical responsibilities include the diagnosis and management of patients with primary immunodeficiency diseases and immune dysregulation disorders.  In addition, he diagnoses and treats individuals with various atopic diseases and asthma.  Dr. Dutmer’s research interests include projects investigating how environmental exposures contribute to asthma severity in urban children.

Dr. Fontenot is the Division Head and Professor of Allergy & Clinical Immunology. The interests of the Fontenot laboratory are diverse, but mainly center on the role of T cells in the development of lung disease. In particular, the laboratory is interested in determining the mechanism by which CD4+ T cells recognize the beryllium antigen in the context of HLA-DP2. The Fontenot team recently determined the structure of HLA-DP2 and this structure defines a potential beryllium binding site. The immunologic mechanisms involved in the progression from beryllium sensitization and disease as well as the development of biomarkers that could potentially detect this progression in the absence of invasive procedures is also a major interest. The lab is also interested in the alterations in the lung microbiome that characterize the lung in different stages of HIV disease and whether a broadened microbiome could contribute to the early onset of lung disease in HIV-infected patients.

Brian Freed, PhD
Dr. Freed is the Executive Director for ClinImmune Labs and a Professor in the Division of Allergy and Immunology. Brian’s research focuses on the effects of smoking on pulmonary immune responses; HLA epitopes and immune mediated diseases.


Charles H. Kirkpatrick, MD
Dr. Kirkpatrick is a member of the faculty of the Division of Allergy and Clinical Immunology and the Department of Medicine. Charles evaluates patients who are referred to the Anschutz Medical Campus because of unusual susceptibility to infectious diseases or autoimmune diseases.  These studies have led to the recognition of two disorders: long term antibody deficiency, and a ‘new immune deficiency’ in which patients fail to develop high avidity antibodies. Long term antibody deficiency is observed in patients who were treated with Rituximab, an FDA approved drug that targets B-lymphocytes.  He has characterized the defect in B-lymphocyte cytology and function and has developed an effective treatment. Current studies are directed at determining the mechanism(s) that lead to this defect. The ‘new immune deficiency’ is characterized by failure to develop high avidity antibodies. Current studies are aimed at defining the mechanisms of this disorder. In addition, Dr. Kirkpatrick studies immune deficiencies and autoimmunities that are due to haplotype insufficiency. He also evaluates and manages patients with Periodic Fever Syndromes.

Brent Palmer, PhD
Dr. Palmer is an Associate Professor in the Department of Medicine, Division of Allergy and Clinical Immunology and the Director of the ACI/ID (research) and ClinImmune (clinical) Flow Cytometry Facility.  Brent has a long-standing interest the consequences of HIV infection on T cell immunity.  The Palmer laboratory performs translational patient-based studies of T cell exhaustion in HIV-infected individuals as well as humanized mouse models of HIV infection to examine the potential of checkpoint inhibitors, such as Programmed Death I (PD-1), for restoring anti-viral immunity.  The Palmer laboratory also investigates the microbiome and has shown that HIV infection is associated with profound alterations in gut microbiota. The Palmer lab investigates how alterations in gut microbiota effect intestinal immune homeostasis and metabolic disease and uses diet modification to remediate effects of dysbiosis on HIV-associated comorbidities and disease.  Dr. Palmer is also interested in the gut-lung axis and mechanisms by which enteric microbes shape pulmonary immunity.
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 ANESTHESIOLOGY

Eric Clambey, PhD
Dr. Clambey is an Assistant Professor in Anesthesiology, focused on immunology research.  Eric’s research is focused on the microenvironmental regulation of T cell responses, including how T cells are influenced by local variation in nutrients/metabolites, including oxygen.  While much of his research has historically focused on mouse models of infection and inflammation, he is increasingly involved with the Lung Cancer SPORE group on the CU Anschutz Medical Campus, including a recently funded pilot mechanism to investigate the role of CD8 T cells in lung cancer.  These studies will include studies on immunotherapy in mouse models of lung cancer, and initial studies characterizing human T cell populations in the human lung by CyTOF.

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 BIOCHEMISTRY & MOLECULAR GENETICS

James DeGregori, PhD
Dr. DeGregori is a Professor in the Department of Biochemistry and Molecular Genetics. James’ lab is interested in understanding how mutational landscapes change in human hematopoietic stem and progenitor cells as humans age, and the influence of lifestyle on these changes. The DeGregori lab is particularly interested in how aging influences selection for potentially oncogenic mutations, and the role of chronic inflammation in this altered adaptive landscape.


Robert Sclafani, PhD
Dr. Sclafani is a Professor of Biochemistry and Molecular Genetics, a Program Director of Cell Biology in the Cancer Center, and the Molecular Biology Graduate Program Director at the University of Colorado School of Medicine. His lab studies cell cycle regulation of DNA replication, DNA repair and mutagenesis and DNA damage checkpoint control in both yeast and human cancer cells. Recently, the Sclafani lab found the chemopreventive agent resveratrol prevents cancer by producing DNA replication stress and DNA damage in FANC/BRCA defective Head and Neck Cancer cells.  As the co-program director of the Cancer Cell Biology program with Dr. Antonio Jimeno, Dr. Sclafani actively supports many members within the program who are investigating immunotherapy in cancer.
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 BIOENGINEERING

Danielle Soranno, MD
Dr. Soranno is an Assistant Professor in Pediatrics, Bioengineering and Medicine at Children’s Hospital Colorado. Danielle uses injectable hydrogels for local and sustained delivery of therapeutics (IL-10, anti-TGF-B, and mesenchymal stem cells) to mitigate the pro-inflammatory, pro-fibrotic immune response following acute kidney injury. The gels/therapeutics are either injected under the kidney capsule or subcutaneously and their location is tracked over time with non-invasive imaging. Dr. Soranno studies these effects in a mouse model of acute-to-chronic kidney disease and monitors them for improvement in kidney function and histological outcomes.
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 CARDIOLOGY

Scott Auerbach, MD
Dr. Auerbach is a pediatric transplant cardiologist interested in immunotherapies as ways to both prevent and treat graft rejection and cardiac allograft vasculopathy (CAV) at Children's Hospital Colorado. Scott is specifically interested in ways to decrease circulating levels of Anti-HLA antibodies in children who are candidates for cardiac transplantation and in transplant patients with antibody mediated rejection, immune mechanisms of CAV development, and single nucleotide polymorphisms (SNPs) leading to variation in immune response. Additionally, Scott has been researching microRNA as biomarkers of cardiac allograft vasculopathy.


Michael Yeager, PhD
Dr. Yeager is an Assistant Professor within the Department of Pediatrics Section of Cardiology, the Department of Bioengineering, and the Linda Crnic Institute for Down Syndrome. Michael’s lab has extensive experience in the study of fibrotic vascular remodeling in the lung and right ventricle (RV), particularly in the settings of pulmonary hypertension (PH) and pulmonary fibrosis associated with systemic sclerosis and autoimmune disease. Most recently, Michael’s research has focused on the role that lymphatics and bronchus-associated tertiary lymphoid tissue (BALT) play with regard to inflammatory and autoimmune fibrotic remodeling. The Yeager lab utilizes human tissue and rat models to study fibrotic lung disease, and assess treatment efficacy using hemodynamic measurements (invasive and non-invasive), as well as histological, cell, and molecular methods. Published and preliminary data raise the possibility that BALT-mediated production of anti-fibroblast autoantibodies drive the pulmonary vascular remodeling and RV failure in PH. In this context, the primary focus area is on the mechanisms governing these complicated processes with the eventual goal of therapeutic intervention.
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 DERMATOLOGY

Mayumi Fujita, MD, PHD
Dr. Fujita is a Professor in the Department of Dermatology at the University of Colorado Anschutz Medical Campus, and a physician at the University of Colorado Hospital and the Denver Veterans Affairs Medical Center. Mayumi’s lab is interested in understanding biological roles and molecular regulations of 1) IL-1 family members such as IL-1b and IL-37, inflammasomes and autoinflammation and 2) tumor heterogeneity in melanoma and its therapeutic resistance.

David Norris, MD
Dr. Norris is a Professor and Chairman in the Department of Dermatology at the University of Colorado in the School of Medicine. David’s clinical interests focus on autoimmune skin diseases such as vitiligo, alopecia areata and systemic lupus erythematosus as well as immunobullus diseases, psoriasis, acne, skin cancer, melanoma and cutaneous lymphoma, pigmentary disorders. David’s research interests are multi-faceted and include cytotoxic mechanism in cutaneous disease, melanoma resistance to apoptosis, control of the migration of melanoma and resistance to activation-induced cell death in T cell lymphoma.

Dennis Roop, PhD
Dr. Roop is the Director of the Gates Center for Regenerative Medicine and Stem Cell Biology and a Professor of Dermatology. The Roop laboratory has a long standing interest in identifying genes required for normal skin development and understanding how they function.  The Roop team discovered that defects in some of these genes cause inherited skin diseases characterized by a very fragile skin, which blisters easily and may result in neonatal death.  Defects in other genes required for normal skin development predispose individuals to develop skin cancer. Current focus is on the generation of induced Pluripotent Stem Cells (iPSCs) from patients with inherited skin fragility syndromes using methods which do not require viral vectors, and determining whether genome editing techniques can be used to correct the genetic defect in these patient-specific iPSCs. The ultimate goal is return keratinocytes derived from genetically corrected iPSCs to the same patient as an autograft.  Another focus is the isolation and characterization of skin cancer stem cells.  An improved understanding of cancer stem cells could result in the development of novel therapeutic strategies that specifically target cancer stem cells for destruction and prevent tumor recurrence.
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 ENDOCRINOLOGY

​Jed Friedman, PhD
Dr. Friedman is a Professor of Pediatrics, Biochemistry & Molecular Genetics, a Professor of Medicine in the Division of Endocrinology, Diabetes, and Metabolism, a Professor of Basic Reproductive Sciences, the Director of the Colorado Program in Healthy Development, and the Director of the NIH Molecular and Cellular Analytical Core Laboratory and NIH Nutrition Obesity Research. Jed is interested in the development of the infant microbiome and its impact on inflammatory pathways in newborn infants, and using germ-free mice to determine mechanisms for monocyte programming to macrophages and metabolic outcomes.

Jena French, PhD
Dr. French is an Assistant Professor of Medicine in the Division of Endocrinology, Diabetes, and Metabolism.  She works in collaboration with Dr. Bryan Haugen, the chair of Endocrinology and thyroid cancer expert, to characterize the immune response in patients with advanced thyroid cancer.  Thyroid cancers have long been associated with concurrent autoimmune disease and encompass a broad spectrum of disease, from relatively indolent tumors to persistent metastatic disease and highly aggressive anaplastic thyroid cancer. This work largely relies on fresh and archived patient samples.  Previous studies by the French laboratory identified PD-1/Tim-3+ T cells in metastatic thyroid cancer.  Their research has led to the development of a multi-center phase II clinical trial that will test the efficacy of pembrolizumab (anti-PD-1) in combination with lenvatinib (anti-VEGFR) in patients with radioiodine refractory disease.  Current studies are focused on developing an immune competent orthotopic mouse model of thyroid cancer where the primary tumor is surgically removed after initial establishment and metastasis. This model would provide a physiologically relevant model of metastatic disease in which to investigate novel combination therapies that target both the tumor and the immune system.


Dr. Haugen is a Professor of Medicine and Pathology and is the Head of the Division of Endocrinology, Metabolism & Diabetes. Bryan’s research interests include molecular studies of thyroid neoplasm diagnosis and pathophysiology as well as the study of molecular therapeutic targets.  Specific areas of research include nuclear hormone receptors (RXR, TR, PPAR) and kinase signaling pathways as therapeutic targets in thyroid cancer, as well as proteomic approaches to molecular markers in thyroid neoplasms.  The Haugen research group is also actively studying novel regulation of the hypothalamic-pituitary-thyroid axis.

Kimber Simmons, MD, MS
Dr. Simmons is an Assistant Professor in Pediatric Endocrinology and Diabetes at Children's Hospital Colorado and the Barbara Davis Center. Kimber’s overall career goal is to become an independent physician scientist studying the clinical immunology of autoimmune disease, with a focus on type 1 diabetes (T1D). Having lived with T1D for over 25 years, Kimber aims to make a fundamental contribution to the prevention of and ultimately a cure for T1D. Her current research focuses include 1) screening children in the general population for type 1 diabetes islet autoantibodies (early stage of type 1 diabetes), 2) understanding the role of adaptive immunity in disease progression (specifically B and T cells) 3) helping to develop preventative therapies for islet autoantibody positive individuals, 4) acting in the role of an investigator for clinical prevention trials, including those that are conducted as part of TrialNet and the Immune Tolerance Network .

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 EPIDEMIOLOGY

Andrea Steck, MD
Dr. Steck is an Assistant Professor of Pediatrics at the Barbara Davis Center for Diabetes. Andrea’s primary research focus is in the area of epidemiology, prediction and prevention of type 1 diabetes. She has a background in pediatric endocrinology, with specific training and expertise in pediatric diabetes. Her research experience includes work with epidemiological studies such as DAISY (Diabetes Autoimmunity Study in the Young), TEDDY (The Environmental Determinants of Diabetes in the Young) and the Twin Family Study.  Dr. Steck is also the Colorado Principal Investigator (PI) for several TrialNet studies, including the TrialNet Pathway to Prevention Study, the TrialNet Oral Insulin Trial and the LIFT (Long-Term Investigative Follow-Up in TrialNet) Study.
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 GASTROENTEROLOGY/HEPATOLOGY

​Edwin de Zoeten, MD, PhD
Dr. de Zoeten is an Associate Professor of Pediatrics Gastroenterology, Hepatology and Nutrition and the Director of the Pediatric Inflammatory Bowel Disease Center at Children’s Hospital Colorado. Ed’s interests focus on the role of the immune system in inflammatory bowel diseases.

Glenn Furuta, MD
Dr. Furuta is a Professor of Pediatrics Gastroenterology, Hepatology and Nutrition and the Director of the Gastrointestinal Eosinophilic Diseases Program at Children’s Hospital Colorado. Glenn’s interest focuses on the role of eosinophils in gastrointestinal health and diseases. Eosinophils normally reside in all of the gastrointestinal mucosa, except for the esophagus, but their role in innate mechanisms of defense and in the pathogenesis of disease is uncertain. The clinical, translational and basic studies of the Furuta lab seeks to provide new insights into these important roles.


Beth Tamburini, PhD
Dr. Tamburini is an Assistant Professor in the Department of Medicine – GI/Hepatology. Beth is interested in understanding the contribution of the lymphatic vasculature to the modulation of immune function in infection, chronic liver diseases, and metastatic cancer.  Beth is currently working on understanding the role of PD-L1 expression on lymphatic endothelial cells and how that modulates immune function using both mouse models and human tissue samples.
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 HEMATOLOGY/ONCOLOGY/BONE MARROW TRANSPLANT

Nick Foreman, MD
Dr. Foreman is a Professor of Pediatrics, the Associate Section Head for Research Pediatric Hematology/Oncology/Bone Marrow Transplant (BMT), and the Seebaum-Tschetter Chair of Neuro-Oncology. Nick performs research on the immunobiology of ependymoma in childhood that has resulted in immunotherapy trials for this tumor.


Lia Gore, MD
Dr. Gore is the Section Head for Hematology Oncology and Director for the Center for Cancer and Blood Disorders at Children's Hospital Colorado and a Professor in the Department of Pediatrics, Medical Oncology and Hematology at the University of Colorado School of Medicine. Lia’s clinical and research interests include developing novel therapies for acute leukemias, with an emphasis on children and young adult patient populations.  Lia was the North American Principal Investigator (PI) for the pediatric trial of the novel bi-specific monoclonal antibody blinatumomab, which helped lead this agent to FDA approval in December 2014.  Lia is the PI of trials of immunotherapeutic agents for childhood cancers including the use of CAR-T cells for refractory leukemias.


Jonathan Gutman, MD
Dr. Gutman is an Associate Professor in the Division of Hematology and the Director of the adult allogeneic stem cell transplantation program.  Jon’s research interests include cord blood transplantation and its unique immunologic features as well as immune manipulation to optimize stem cell transplant and cellular therapies.  Jon is actively involved in the development of the University’s CAR T cell program and has specific interest in checkpoint inhibition.


Dr. Jordan is a Professor of Medicine and the Division Chief of Hematology. Craig’s research has been focused on characterization and targeting of leukemia stem cells (LSCs).  In leukemia, like many forms of cancer, a small subset of so-called “cancer stem cells” are thought to be key drivers of pathogenesis and relapse.  While therapies that reduce bulk tumor have been devised for many forms of cancer, effective eradication of cancer stem cells is more challenging, and represents an important goal towards improved therapies.  In the most prevalent forms of adult acute leukemia, long-term survival rates are only ~20%, hence, better therapies are urgently needed. The Jordan laboratory was the first to describe properties of human LSCs that are relevant to therapeutic targeting. These observations have led to multiple clinical trials using antibodies, small molecules and cell-based immunotherapies designed to target the biological properties first reported from our studies. Building on our initial basic science studies, in subsequent years we developed drug screening and identification methods to identify improved therapeutic agents to target LSCs.

Alisa Lee-Sherick, MD
Dr. Lee-Sherick is a Pediatric Bone Marrow Transplant specialist at Children's Hospital Colorado. The primary focus of Alisa’s research is to harness the immune system to more effectively cure acute leukemia.  Alisa and her lab explore the role that monocytes and macrophages play in immune evasion of leukemia and how this can be reversed.  One such approach is by inhibiting MERTK (a protein on monocytes and macrophages that promotes cancer growth and metastasis), which results in an anti-tumor microenvironment and decreases immune evasion. The hope is that the knowledge gained from this research can be used to develop novel immunotherapeutic approaches to treat acute leukemias.

Taizo Nakano, MD
Dr. Nakano is an Assistant Professor of Pediatrics and the Medical Director for the Vascular Malformation and Tumor Center for Cancer and Blood Disorders. As a clinical hematologist, Taizo’s world revolves around the normal and abnormal function of hematopoietic cells.  Although, on their own, these cells cause vast disease in patients that he sees and treats daily, they go on to directly influence every component of the immune system and become key players in immunodeficiency, autoimmunity and immune regulatory disorder.  The care and treatment of many populations under his care (including Bone Marrow Failure, Immune Thrombocytopenia, Immunodeficiency, Auto- and Allo-immune disorders, and Hemophagocytic Lymphohistiocytosis) is influenced by the growing role the immune system is now known to have in the contribution of disease and what role it plays in the treatment of disease.  The Nakano group carries out retrospective and prospective interventional trials to better understand and advance treatment options for these hematologic disorders.  Ongoing clinical collaborations with pediatric immunology and pediatric rheumatology have strengthened the group’s ability to evaluate and study rare immunohematologic disorders.  The goal is to promote clinical communication, collaboration and translational research to provide optimal and novel therapies to every patient.

Eric M. Pietras, PhD
Dr. Pietras is an Assistant Professor in Hematology with a research focus on hematopoietic stem cell (HSC) biology. The Pietras lab focuses on understanding how inflammation affects the fate decisions of HSCs, resulting in dynamic blood output in response to injury, infection and other physiological conditions. The lab also has significant interest in how chronic inflammatory diseases such as rheumatoid arthritis, lupus and obesity ‘remodel’ the blood and immune systems in ways that can worsen disease outcomes, as well as how exposure to inflammatory signals impacts the function of HSCs during transplantation.

Enkhtsetseg ‘Enkhee’ Purev, MD, PhD
Dr. Purev is an Assistant Professor in the Department of Medicine Blood Cancer and BMT Program. Enkhee’s research is focused on cellular Immunotherapy that involves manipulating immune cells to identify and kill cancer cells.  This is achieved by genetic manipulation of immune cells, in a laboratory setting, to attack specific targets on malignant cells.  These modified immune cells, called chimeric antigen receptor T-cells (CAR-T), are then introduced to the patients where they seek out and kill malignant cells presenting the same targets. Enkhee is currently developing and studying CD19, CD123, and CD19/20 dual CARs with hopes to extend the targets in the future. Dr. Purev aims to build the infrastructure that enables us to efficiently develop, study, and manufacture personalized, targeted modality of cell-based treatment.

Jenna Sopfe, MD
Dr. Sopfe is a Pediatric Hematology/Oncology/BMT Fellow at Children’s Hospital Colorado and the University of Colorado. Jenna's research focuses on malglycemia (defined as hyperglycemia, hypoglycemia and glycemic variability) in the pediatric stem cell transplant population. She is attempting to define the incidence and consequences of malglycemia in this population through retrospective and prospective cohort studies. Outcomes may include worsened mortality and risk of infections and GVHD, which have been described in adults. It is postulated that these associations may be related to immune dysregulation that is known to occur with malglycemia.

Dr. Verneris is a Professor of Pediatrics – Hematology/Oncology and Bone Marrow Transplantation and the Director of Bone Marrow Transplant and Cellular Therapy. Mike’s clinical interests include the use of transplantation for acute leukemia, double umbilical cord blood transplantation, graft-versus-leukemia and immune reconstitution. The Verneris laboratory is focused on using cellular therapy to treat cancer and other diseases and associated research is in two broad areas: lymphocyte differentiation and lymphocyte biology and immune-based cancer therapies. In the context of lymphocyte differentiation, the Verneris lab seeks to understand the conditions, signaling pathways and developmental intermediates that stem cells go through during lymphocyte differentiation.  Research has focused on the differentiation of innate lymphoid cells (NK cells and ILC3) using established embryonic and induced pluripotent stem cells, as well as hematopoietic stem cells derived from cord blood and bone marrow. In the context of lymphocyte biology and immune-based cancer therapies, the Verneris lab has focused on redirecting the immune system to cancer. Studies include the use and development of bi- and trispecific immune killer engagers (BiKes and TriKes) and chimeric antigen receptors (CARs).  The Verneris team has also discovered how to differentiate stem cells to NK cells and ILC3 cells and are using drugs and genetic screens to enhance the development and function of these cells.  The long-term goal is to have an “off the shelf” “living drug” that can be used to mitigate graft vs. host disease, inflammatory bowel disease and cancer.
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 IMMUNOLOGY - BASIC

John Cambier, PhD
Dr. Cambier is a Distinguished Professor & Chairman for the Department of Immunology & Microbiology and the Director of the Human Immunology and Immunotherapy Initiative (HI3). The Cambier lab is currently focused on four specific problems related to tolerance and autoimmunity:  1) the basis of antigen unresponsiveness of anergic B cells, and mechanisms underlying loss of  anergy leading to autoimmunities such as Lupus, Type 1 Diabetes and Rheumatoid Arthritis, 2) the role of autoantigen avidity and affinity in determining alternate molecular bases of anergy, 3) the mechanism of signal regulation by feedback mechanisms and inhibitory receptors such as FcγRIIB, 4) the function of STING/MPYS, a recently described innate signaling adaptor cloned in the Cambier laboratory.
 
Initial studies involving isolation and functional analysis of autoantigen-specific B cells from healthy and autoimmune mice and humans have focused on the status of insulin-specific B cells Type 1 Diabetes, and indicate that in both mice and humans anergy to this autoantigen is lost long before onset of disease, but regained in humans within one year of diagnosis. These studies suggest an important role for environmental factors such as infection and injury in predisposing individuals to autoimmunity. Future work in this area will expand studies to other autoimmunities, and define signaling mechanisms that maintain anergy, and fail during development of autoimmunity. Parallel studies seek to understand whether and how environment factors such as infection and injury defeat tolerance mechanisms.

Sean Colgan, PhD
Dr. Colgan is a Professor of Medicine and Immunology, the Director of the Mucosal Inflammation Program, and the Chief of the GI and Liver Innate Immune Programs at the University of Colorado School of Medicine. Sean’s laboratory is interested in defining novel innate immune factors that promote inflammatory resolution, with a specific focus on the gastrointestinal tract. Their work has integrated the role of the tissue microenvironment in host-microbe interactions, shifts in tissue metabolism and the oxygen utilization as endpoints for analysis. These studies employ molecular, cellular and translational models to define these principles.

Howard Davidson, PhD
Dr. Davidson is an Associate Professor of Pediatrics and Immunology and Microbiology at the Barbara Davis Center for Childhood Diabetes. Howard’s laboratory focuses on the role of adaptive immunity in type 1 diabetes (T1D). The current emphasis is focused on understanding the role of autoimmunity to the beta cell protein ZnT8 in T1D pathogenesis, and developing/validating T cell based biomarkers for improved patient stratification and monitoring of therapeutic efficacy.

Claudia Jakubzick, PhD
Dr. Jakubzick is an Assistant Professor in the Department of Pediatrics at National Jewish Health and the Department of Immunology and Microbiology at the University of Colorado Anschutz. Claudia’s research focuses on three projects. The first project is focused on the human respiratory system, which is the body’s largest interface exposed to ambient air, and it continuously encounters particles, allergens and microbes. The aims of this project are to functionally characterize human pulmonary dendritic cells in the lung and lung-draining lymph nodes, which play crucial roles in lung immunity against foreign material, with the hopes that we will gain insight into designing new vaccines and developing novel immune therapies, including the treatment of forms of cancer that are now incurable. The second project focuses on how the immune system recognizes and responds to minor antigens (mAgs) produced by cancerous tumors. The immune system has evolved to recognize mutations and alterations of minor antigens (mAgs) produced by cancerous tumors, but this adaptive immune response carries costs: The immune system can reject the body’s own tissues, as occurs in autoimmune disorders, or other needed tissues, as with organ transplantation. We do not yet understand how endogenous antigen-presenting cells recognize, coordinate and induce immunological responses against mAg-mismatched cells, particularly in the absences of pathogen-associated molecular patterns (PAMPs) that mark foreign agents. If we can uncover the sequential cellular cascade that leads to mAg-mismatched cell rejection, then we can design drugs to prevent tissue rejection, with benefits for transplant surgery, autoimmune disorders, and more. The third project is focused on cancer, one of the most enduring health problems of the modern era. A major new direction in cancer treatment is the development of anti-cancer vaccines, which would educate the body’s immune system to recognize and kill cancer cells. If successfully developed, vaccines could provide long-lasting or permanent remission of a cancer without requiring radiation, chemotherapy, or other treatments with adverse long-term effects.  The Jakubzick lab has projects that lay a scientific foundation for developing anti-cancer vaccines based on selective targeting of dendritic cells, which can train other parts of the immune system to destroy tumor cells.  We have recently discovered that educating a specific type of dendritic cell in a particular way elicits an immune response that nearly completely eliminates metastatic cancer in the lungs of mice. The goal of our current project is to characterize and outline the fundamental mechanism of this system. Achieving this goal will provide critical steps towards developing this approach as a treatment for cancer in humans.

John Kappler, PhD
Dr. Kappler is a Distinguished Professor of Immunology and Microbiology. For the past 10+ years the Kappler laboratory at National Jewish Health has been in an extended collaboration with members of the Basic and Translational Research Division at the Barbara Davis Center (BDC) trying to understand the molecular basis CD4+ T cell recognition of pancreatic islet protein epitopes in type 1 diabetes (T1D). The research collaboration with the Basic and Translational Research Division at the BDC has been very productive, especially in studies on insulin as a primary target from CD4+ T cells in T1D in mouse and man and on chromogranin A (ChgA), another pancreatic protein targeted in T1D in the mouse and perhaps in humans. Our research has shown that the natural peptides derived from these proteins, are targeted by diabetogenic CD4+ T cells in the NOD mouse model of the disease, but are in fact very weak antigens.  We have shown that a few particular amino acids can be added to one end of the insulin peptide or to the other end of the ChgA peptide to increase their potency more than 1000-fold. Working with the laboratory of Dr. Shaodong Dai at National Jewish Health, we were able to use X-ray crystallography to determine the molecular basis for how these additions accomplish this dramatic increase in immunogenicity.  Subsequently, for insulin, experiments by Drs. Nakayama, Gottlieb, Michels, Sosinowski and Davidson, some in collaboration with researchers at the Benaroya Center in Seattle have shown a similar mutational improvement in recognition of the insulin peptide by CD4+ T cells from human patients with type-1 diabetes.
These findings have led us hypothesize that these types of modifications may naturally occur uniquely in the pancreas by a process called transpeptidation accounting for the initiation of T1D in both mouse and man.  Since such a modification creates a “neo-antigen” never seen by the immune system before, the immune system may mistake the peptide for a “foreign” antigen and mount a response.  Testing this hypothesis is a major goal of our present research.

Ross Kedl, PhD
Dr. Kedl is a Professor in the Department of Immunology & Microbiology. Ross’ lab is interested in the curious boundary between the innate and adaptive immune systems and seeks to elucidate signals and pathways emanating from the various families of innate receptors most efficiently mediate the transition to the adaptive cellular immune response.  The Kedl lab seeks to determine not only the basic rules of immunity, many of which remain elusive, but also to identify practical methods of intervention for the purposes of vaccine discovery, development and design.  Experimentally a number of ways in which the innate pathways intersect with the TNF receptor/Ligand superfamily have been demonstrated, resulting in potent T cell expansion, effector function, and memory generation. These discoveries and novel vaccination methods are being applied to both viral and tumor model systems in an effort to develop clinically relevant methods of therapeutic vaccination against diseases such as chronic infections and cancer.

Laurel Lenz, PhD
Dr. Lenz is a Professor in the Department of Immunology and Microbiology. His research focuses on dissecting endogenous and pathogen-derived mechanisms for regulation of inflammatory and immune responses. His translational work includes the identification, development, and optimization of polypeptides and small molecules that can be used to regulate the activities of myeloid and natural killer immune cells. His group is actively engaged in dissecting the mechanisms of action for these factors and their potential for therapeutic use in cancers, infections, and inflammatory diseases.

Roberta Pelanda, PhD
Dr. Pelanda is a Professor in the Department of Immunology and Microbiology and the Director of the Translational Research Networking and Preclinical Models (TRNPM) facility in the Human Immunology and Immunotherapy Initiative (HI3). Roberta’s interests in human immunology are in improving our understanding of the origin and characteristics of autoantibody-producing human B cells with the goal of developing novel immunotherapies for lupus and similar autoimmune diseases. Roberta’s lab and the core she directs develop mice bearing a human immune system (hematopoietic humanized mice). These animals are utilized to investigate the function of the human immune system in pathological contexts (e.g., the immune response to cancer) and to develop and test novel immunotherapies.

Dohun Pyeon, PhD
Dr. Pyeon is an Associate Professor in the Department of Immunology and Microbiology and the Department of Medicine. Human papillomaviruses (HPVs) are causally linked to over 5% of all human cancers, including nearly all cervical cancer and ~25% of head and neck squamous cell carcinoma (HNSCCs), resulting in half a million deaths every year. The Pyeon lab has recently discovered that the HPV oncoprotein E7 epigenetically dysregulates chemokines and MHC-I expression, leading to suppression of antiviral and antitumor immune responses. Current research continues on investigating the mechanisms of immune dysregulation by HPV during HPV-associated cancer progression in order to develop effective immunotherapies for HPV-positive cancers.

Dr. Rochford is Professor in Immunology and Microbiology at the Anschutz Medical Campus. Rosemary’s laboratory does research on two human pathogens, Epstein-Barr virus (EBV) and Plasmodium falciparum as well as studies on their etiologic link to Burkitt's lymphoma (BL), the most common childhood cancer in Sub-Saharan Africa. She has completed 2 longitudinal birth cohorts in Kenya to address the question of why P. falciparum malaria infection of infants is linked to BL. Her studies have uncovered a number of ways that repeated infection with P. falciparum malaria, a feature in areas where malaria transmission is holoendemic, dysregulates EBV infection and immunity, ultimately increases the risk for BL in children. Current research is now focusing on how Plasmodium infection dysregulates B cell function and activates the enzyme Activation Induced cytidine Deaminase (AID). She has also found that a second strain of EBV that is common in Africa can infect T cells. Her laboratory is working to understand how this virus gains entry to T cells and the potential role this has in the pathogenesis of EBV-associated malignancies. A second major area of study in her laboratory is the use of a pre-clinical humanized mouse model to test for hemolytic toxicity of anti-malaria drugs in the context of glucose phosphate 6 dehyrogenase (G6PD) deficiency, the most common hemoglobinopathy in the world. Primaquine is the only licensed drug to treat the liver stage of malaria and it could be a potential tool for malaria eradication efforts. However, people with G6PDd are at risk for developing hemolytic anemia if treated with primaquine necessitating the development and testing of new variants of primaquine that do not cause hemolytic anemia. She is developing this model to further study Plasmodium infection in G6PDd hosts.

Jill Slansky, PhD
Dr. Slansky is a Professor in the Department of Immunology and Microbiology and the Director of the Human Immune Monitoring Shared Resource (HIMSR) core facility in HI3. Jill’s research interests globally focus on how to better harness and stimulate T cells of the immune system to mediate a more effective anti-tumor response. Currently, Jill’s lab is using an animal model for colon cancer and tissue samples from breast cancer patients to characterize T cell responses that are specific to tumors. In the animal model, they recently used genome-wide expression analyses to generate a molecular profile of tumor-specific tumor-infiltrating T cells. Interestingly, this study showed that the T cells from the tumor more closely resembled “self-tolerant” T cells than “exhausted” T cells. Using human samples they recently identified a panel of T cell receptors that were shared among different breast cancer patients, but not control donors. The identification of cognate antigens and mimotopes for these T cells is underway using soluble versions of the T cell receptors to screen peptide-antigen libraries and breast cancer cell lines.

Tomasz Sosinowski, PhD
Dr. Sosinowski is an Instructor in the Davidson laboratory within the Barbara Davis Center. Tomasz’s main focus is the development of reagents and assays for studying human antigen-specific T cells. Since 2013 Tomasz has been working on developing an assay for the detection of auto-antigen specific CD4+ T cells in Type 1 Diabetic subjects. He has found that this particular assay is an improvement over the traditional ELISPOT for testing viral responses and autoreactivity, and is confident that it can be expanded to other systems, including other autoimmune diseases and potentially cancer.

Raul Torres, PhD
Dr. Torres is a Professor in the Department of Immunology and Microbiology and the Director of the Graduate Program in Immunology. Raul’s research interests have historically focused on fundamental aspects of B cell development and antibody response, primarily relying on wild type and genetically-engineered mouse models. Through the course of these studies, Raul and his lab have identified new mechanisms that 1) regulate B cell humoral immunity to HIV and 2) tumors exploit to suppress CD8 T cell tumor immunity. Raul’s interests in human immunology and immunotherapy, and the Human Immunology and Immunotherapy Initiative, are to establish collaborations that will allow proof-of-principal pre-clinical and, eventually, clinical studies that improve antibody responses to HIV and tumor immunity.

Linda van Dyk, PhD
Dr. van Dyk is Vice Chair and Associate Professor in the Department of Immunology and Microbiology. Research in the van Dyk lab focuses on molecular interactions between virus and host, focused on a group of viruses that results in lifelong latent infection and causes a variety of tumors in conditions of immune suppression.  Using a mouse model, the van Dyk team has learned that a virus encoded cyclin is required for reactivation of latent virus, a critical point in tumorigenesis and in potential antiviral therapeutics.  This viral cyclin antagonizes a host tumor suppressor, p18Ink4c or cdkn2c, which is important in control of latent virus infection and in a variety of sporadic tumors.  The van Dyk lab also studies small non-coding RNAs of viral origin in regulating both virus and host in inflammatory disease and tumorigenesis.  Our interests in the human immunology and immunotherapy initiative are two-fold:  first, to use our mouse model to test the effects of immunotherapy on control of chronic ongoing virus infections and second, to further our understanding of cyclin/tumor suppressor interactions and small non-coding RNA effects in human tumors associated with Epstein Barr virus and Kaposi’s sarcoma associated virus.

Jing Wang, MD, PhD
Dr. Wang is an Assistant Professor within the Department of Immunology and Microbiology interested in elucidating the mechanisms of immune evasion in B cell lymphomas or head neck squamous cell carcinomas (HNSCC). Jing’s research lab has established a mouse B cell lymphoma and HNSCC models which harbor defects in DNA repair and appear to evade the recognition of T or NK cells. Dr. Wang and her research team are interested in uncovering the relevance of their findings in human patients.
11

 IMMUNOLOGY - CLINICAL

Peter Gottlieb, MD
Dr. Gottlieb is a Professor of Pediatrics and Medicine within the Barbara Davis Center for Diabetes. The Gottlieb laboratory projects are designed to advance basic knowledge of the immune response to autoantigens in type 1 diabetes with the goal of designing immunotherapies for prediabetes and new onset type 1 subjects. The research is designed to better understand the molecular interaction between MHC molecules, antigens and T cell receptors that lead to the selection of antigen-specific T cells.  In addition, understanding the relationship of autoreactive vs. T regulatory cells has been an important component of this work and, more recently, understanding how other immune system functions, such as innate immunity, may alter the balance and threshold between regulation and pathogenicity as well.

Elena Hsieh, MD
Dr. Hsieh is an Assistant Professor of Immunology and Microbiology and Pediatrics. The goal of the research in Elena’s laboratory is to elucidate cellular and molecular mechanisms underlying immune derangements in the pathogenesis of pediatric autoimmune, inflammatory and immunodeficient disorders, which would provide the foundation for novel disease biomarkers to prognosticate disease activity, and select therapeutic interventions.

Holger Russ, PhD
Dr. Holger Russ is an Assistant Professor of Pediatrics at the Barbara Davis Center and a faculty member of the Gates Center for Regenerative Medicine. Holger was part of a team of scientists to demonstrate the successful generation of thymic epithelial progenitors (TEPs) in vitro from human pluripotent stem cells for the first time. TEPs further mature into thymic epithelial cells with the ability to rescue T-cell development in vivo. However, critical aspects of human thymus development, T-cell selection and interaction with other tissue compartments (e.g. tumors and autoimmune affected cell types) are poorly understood and appropriate models to illuminate these processes are unavailable.  Currently, the Russ research team has combined their direct differentiation protocols with gene editing technologies to establish novel model systems, both in vitro and in vivo, to answer these questions in a strictly human context.

Aaron Michels, MD
Dr. Michels is an Associate Professor of Pediatrics & Medicine, the Frieda and George S. Eisenbarth Clinical Immunology Endowed Chair, and Director of Clinical Immunology at the Barbara Davis Center. The Michels’ laboratory at the Barbara Davis Center for Diabetes is focused on studying the immunology of autoimmune diseases, with a particular focus on type 1 diabetes. Basic and translational research focuses on understanding the underlying immunology of diabetes and how human leukocyte antigen (HLA) alleles confer disease risk and protection. The Michels’ lab discovered that small ‘drug-like’ molecules targeted to MHC class II antigen presentation can block T cell responses and they have translated this therapeutic approach from bench to bedside to block a diabetes susceptible MHC class II molecule.  Studies are ongoing to understanding the mechanism by which dominant protection is afforded from diabetes resistant MHC class II molecules in animal models and humans.
12

 INFECTIOUS DISEASE

Ed Janoff, MD
Dr. Janoff is a Professor in the Division of Infectious Disease in the CU School of Medicine and the Director of  Mucosal and Vaccine Research Colorado.  The Janoff lab focuses on diseases of international importance, such as diarrheal disease, respiratory infections, and HIV-1/AIDS. The research team characterizes mucosal responses to Streptococcus pneumoniae in the lung and to HIV-1 in the intestine, reproductive tract, and in breast milk. Each study is supported by a field site in Africa (Uganda, Burkina Faso, Botswana and South Africa) with collaborators from these African nations, the U.S. and Europe. The goal of the Janoff laboratory is to provide a scientific foundation for mucosal vaccines to prevent pneumococcal infections and transmission of HIV-l /AIDS. Clinical and basic laboratory approaches are integrated to determine how pathogens interact with the host at the mucosal surface and how innate and humoral mechanisms, individually and in concert, serve to protect against infection. The Janoff lab’s primary model for mucosal defense against HIV involves post-natal transmission of the virus by breast milk and the characterization of the mechanisms by which pathogen-specific antibodies in blood and milk from transmitting and non-transmitting mothers in Burkina Faso, Botswana and Uganda, neutralize autologous and heterologous HIV isolates using cellular, molecular, and biochemical approaches. For S. pneumoniae, systemic and mucosal responses to natural infection and vaccine, the molecular basis for capsule-specific antibody responses (VH gene diversity and mutational pattern), and the functional activity of these human antibodies are characterized. The goal is to develop effective vaccines against these pathogens to prevent infections where they begin, at the mucosa.


Christiana Smith, MD
Dr. Smith is a faculty member in the Department of Pediatric Infectious Diseases. Christy’s faculty appointment involves a combination of translational research and clinical practice. Her interest is in HIV-infected and HIV-exposed infants, children, and adolescents. Christy’s research focuses on immune defects in HIV-exposed, but uninfected (HEU) infants. These infants have increased rates of infections, hospitalizations, and deaths, likely secondary to abnormalities in multiple immune cell types (B cells, T cells, dendritic cells, natural killer cells, etc). The goal is to discover what leads to immune dysfunction in HEU infants so that an intervention can be developed to prevent morbidity and mortality in this population.


Adriana Weinberg, MD
Dr. Weinberg is a Professor of Pediatrics, Medicine, and Pathology and the Director of the Molecular and Virology Clinical Laboratories. As an infectious diseases specialist, Adriana’s research is translational and focused on immune defenses against infectious agents. As such, she has conducted multiple studies focused on the immunopathogenesis of HIV and herpesviral infections; immune responses to vaccines in immune competent and compromised hosts; and the development of molecular tools for the diagnosis and monitoring of opportunistic infections.


Cara Wilson, MD
Dr. Wilson is a Professor of Medicine and Immunology with a primary appointment in the Department of Medicine (DOM) Division of Infectious Diseases and a secondary appointment in the Department of Immunology. Cara is a translational immunologist focused on bench to bedside research primarily in HIV infection and inflammation but also on mucosal immunology of aging.
13

 MEDICAL ONCOLOGY

Antonio Jimeno, MD, PhD
Dr. Jimeno is a Professor in the Division of Medical Oncology in the School of Medicine at the University of Colorado. Antonio has developed an interest in integrating preclinical research, drug development, and clinical research. He has made a special emphasis in 1) developing better preclinical models, particularly humanized mice, 2) determining predictors of response, and 3) devising ways to integrate that knowledge into clinical trials to individualize anti-cancer therapy. His concomitant work in the laboratory and the clinic has materialized in the form of novel inventions (drugs and biomarkers) that are currently the subject of prospective clinical testing. His clinical interest is Head and Neck and Upper Gastrointestinal cancer.

Traci Lyons, PhD
Dr. Lyons is an Assistant Professor of Medicine in the Division of Medical Oncology. Traci’s laboratory focuses on mechanisms of lymphatic mediated metastasis of breast cancer. Specifically, utilizing mouse models to investigate developmentally regulated programs of inflammation and lymphangiogenesis that are utilized in the adult mammary gland and may be hijacked by breast tumor cells. The results of these translational studies have the potential to instruct therapy aimed at prevention of breast cancer metastasis.


Dr. Robinson is a Professor, Division of Medical Oncology at the University of Colorado. Bill is an active clinical and basic investigator studying the molecular and genetic regulation of melanocyte development and melanoma, particularly the role of microRNAs in the regulation of melanoma associated genes. Together with Dr. Lynn Bemis he is investigating the use of nano-technology to detect mutations in cancer cells. He is the founder of the melanoma tissue bank at CU which provides research materials to local investigators as well as numerous national and international collaborators. He also coordinates the Frontiers in Melanoma Seminar Program which brings in invited speakers from around the world for collaboration and discussion.

Wells Messersmith, MD
Dr. Messersmith is Professor and Head, Division of Medical Oncology, Director for the GI Medical Oncology Program and Program co-Leader for Developmental Therapeutics. Wells' lab is mainly focused on using a personalized approach in developing new anticancer drugs for GI cancers. In particular, the lab uses a novel colorectal and pancreatic explant model whereby tumor tissue is obtained from the operating room and then placed directly into mice. Tumors are treated with new drugs and predictive biomarkers of sensitivity are discovered. These predictive markers are used in the clinic to pre-select patients that would most likely derive benefit from these new drugs. Additionally, these tumors are evaluated in orthotopic and metastatic models. Current anticancer drugs in the lab target Notch (g-secretase), Src, and hedgehog pathways.
14

 NEPHROLOGY

Joshua M. Thurman, MD
Dr. Thurman is Professor of Medicine in the Division of Nephrology and Hypertension, and he is the Director of the Glomerulonephritis Program. His laboratory focuses on the immune basis kidney disease. The lab studies the underlying causes of auto-immunity and inflammation, and has developed several novel anti-inflammatory therapeutic agents. Projects are also underway that explore the link between inflammation and cancer. Dr. Thurman’s laboratory has also developed novel radiologic probes to detect and monitor renal inflammation by magnetic resonance imaging (MRI) and positron emission tomography (PET). Dr. Thurman oversees the Glomerulonephritis Clinic at the University of Colorado Hospital. The Glomerulonephritis Clinic cares for patients with all forms of inflammatory kidney disease, and also participates in clinical trials of new therapies and diagnostic tools for treating these diseases.
15

 NEUROLOGY

Jeffrey Bennett, MD, PhD
Dr. Bennett is a Professor of Neurology and Ophthalmology and an active member of the Department of Neuroscience on the Anschutz Campus. The Bennett laboratory performs research in the areas of human neuro-immunology; particularly focused on demyelinating disorders of the central nervous system including multiple sclerosis and neuromyelitis optica. The lab has generated banks of recombinant antibodies cloned from patients with these disorders and have developed animal models to study disease and recovery. Active research grants from the NIH, the National Multiple Sclerosis Society, and the Guthy-Jackson Foundation (NMO Research Foundation) fund studies on immunologic profiles in disease, to develop novel approaches to diagnosis, and to develop new therapeutics.


John Corboy, MD
Dr. Corboy is a Professor of Neurology, the Co-Director for the Rocky Mountain Multiple Sclerosis (MS) Center at the University of Colorado, and the Director of the Rocky Mountain MS Center Tissue Bank. John’s interests are in the diagnosis and treatment of central nervous system (CNS) neuroimmunological conditions, such as Multiple Sclerosis (MS), Neuromyelitis Optica (NMO), N-methyl D-aspartate (NMDA) receptor antibody encephalitis, and a host of paraneoplastic and related conditions.


Gregory P. Owens, PhD
Dr. Owens is a Research Professor in the Department of Neurology at the University of Colorado School of Medicine. Dr. Owens’ research investigates the role of B cell immunity in the pathogenesis of MS.  To better understand the nature of this response, they have used fluorescence-activated cell sorting and single cell PCR to analyze the B and plasma cell populations infiltrating the CNS of MS patients. The features of the B cell repertoire are indicative of a targeted and antigen driven response in MS. They have generated a panel of monoclonal recombinant antibodies from plasma cell clones identified in MS CSF and are using recombinant antibodies for immunological screening to identify disease relevant MS antigens.

Dr. Tyler is a Professor and Chair of the Department of Neurology. Ken’s laboratory uses both in vivo and in vitro models to study the molecular and genetic basis of viral pathogenesis and viral-induced cell death in the CNS. Major current projects include: (1) Identifying differences in patterns of gene expression in the brain and the cognate signaling pathways induced by distinct neurotropic viruses, including reoviruses and flaviviruses (West Nile and Japanese encephalitis virus), in an effort to identify novel therapeutic targets for antiviral therapy; (2) Investigating the neuroinflammatory responses to CNS viral infections, including the activation of astrocytes, microglia and chemokine/cytokine production in experimental models utilizing mice and ex vivo brain and spinal cord slice cultures; and (3) Studying the mechanism of virus-induced CNS apoptosis, including mitochondrial and cell-death mediated pathways, and the impact of modulating these pathways on CNS injury and neuronal death.

Tim Vollmer, MD
Dr. Vollmer is a Professor in the Department of Neurology and Vice Chair of clinical research. Dr. Vollmer is Medical Director of the Rocky Mountain Multiple Sclerosis Center, and Co-Director of the RMMSC at Anschutz, which provides a multidisciplinary approach to treatment of this disease. Dr. Vollmer sub-specializes in multiple sclerosis and has a special interest in immunotherapies for MS. He also collaborates with several basic science laboratories on mechanism of action of newer MS therapies, and is working in collaboration to develop a vaccine approach to MS that involves inducing regulatory B lymphocytes that target CNS antigens. To date, Dr. Vollmer has completed over 100 clinical studies in MS. He is active in the local, regional and international communities conducting research in MS.

David H. Wagner, Jr. PhD
Dr. Wagner is an Associate Professor in the Departments of Medicine and Neurology and the Head of the Immunology Section at the Webb-Waring Center. David’s research involves human Type 1 Diabetes (T1D) and human Multiple Sclerosis (MS) studies. His lab identified one of the pathogenic effector T cell subsets in both diseases, Th40 cells. The Wagner lab is interested in better defining biomarkers, from the T cell perspective in both T1D and MS, and how Th40 cells drive and perpetuate autoimmune inflammation.  David is also developing a small peptide that targets CD40 mediated autoimmune inflammation.

16

 NEUROSURGERY

Michael Graner, PhD
Dr. Graner is an Associate Professor in the Department of Neurosurgery. Michael's research focuses on the immunology and biology of brain tumors. From a clinical perspective, he is interested in vaccine design and implementation, which includes the search for appropriate combinations of therapies to enhance immune responses or to downplay the role of tumor-induced immune suppression.
17

 PATHOLOGY

Jennifer Richer, PhD
Jennifer Richer is a Professor and Co-Director of the Cancer Center Pathology Core. Dr. Richer and her lab have determined that triple negative breast cancers (TNBC) upregulate and utilize the enzymes IDO1 and TDO2 to facilitate production of an immunosuppressive substance, kynurenine. The Richer lab hypothesizes that kynurine acts in an autocrine fashion to bind and act on the aryl hydrocarbon receptor (AhR) in tumor cells to exert an anti-apoptotic effect, while at the same time acts in a paracrine fashion to suppress immune cells, again via AhR, and that this dual action facilitates the clinically aggressive behavior of this subtype of breast cancer. They have determined that indeed, kynurenine decreases proliferation and increases death of primary human CD8 T-cells. The Richer lab is also studying additional effects of this metabolite of the tryptophan catabolism pathway on other types of immune cells involved in the anti-tumor response. Since many immune cells express both AhR and androgen receptors (AR), another area of active investigation focuses on the role of anti-androgens (used to directly target tumor cells) on the immune response.


Fred R. Hirsch, MD, PhD
Dr. Fred Hirsch is a Professor of Medicine and Pathology, the Pia and Fred R. Hirsch Endowed Chair for the University of Colorado Cancer Center, and the CEO for the International Association for the Study of Lung Cancer (IASLC). Fred has worked with clinical/ translational research in lung cancer for more than 25 years. His current interest is in biomarker developments for early detection, chemoprevention and treatment of lung cancer. He is also studying markers related to molecular targeted therapies in order to understand the mechanisms of action and resistance of these new therapies, and to be able to select the patients who will benefit from such treatment. The biomarker studies relate to the development of molecular targeted therapies for chemoprevention and treatment of lung cancer including studies on lung cancer cell lines and tumor tissue from clinical cohorts. Most recently, Dr. Hirsch is leading the “PD-L1 Blueprint Project,” which is supported by the FDA and is a collaboration with several pharmaceutical companies. This study is primarily focused on comparing and harmonizing all clinical PD-L1 assays.
18

 PULMONARY SCIENCES

Kelley Colvin
Kelley is a Senior Professional Research Assistant in a lab that studies lung vascular biology, pulmonary arterial hypertension (PAH) in particular. Understanding the contribution of altered immunity to the pathology of PAH has been a subject of contemplation of many laboratories for years. Although some of the putative autoantigens in autoimmune PAH have been identified, a direct role for autoantibodies in PAH has not been established. The lab has a unique approach that focuses on autoimmune mechanisms, which may directly affect pulmonary vascular remodeling.


Howard Li, MD
Dr. Li is an Assistant Professor in the Department of Medicine, Division of Pulmonary Sciences and Critical Care Medicine. Howard’s research focuses on the role of the tumor microenvironment in lung cancer, with extensive experience in preclinical lung cancer carcinogenesis, chemoprevention, and orthotopic models. Recently, research in the Li lab has focused on the role of PD-L1 on cancer cells and immune cells in the tumor microenvironment on lung cancer progression.


Raphael Nemenoff, PhD
Dr. Nemenoff is a Professor of Medicine and the Director of Research for the Division of Renal Diseases and Hypertension. Raphael’s laboratory is studying the role of the immune system on the progression and metastasis of lung cancer, using an orthotropic immunocompetent model in which murine lung cancer cells are implanted into the lungs of syngeneic mice.  Research within the Nemenoff lab has focused on the role of both the innate and adaptive immune system in regulating disease progression.  Using a panel of murine cell lines responses to immune checkpoint inhibition have been correlated with the nature of the cancer cell.  Ongoing studies have also used RNA-seq to profile macrophage populations in this model.
19

 RADIATION ONCOLOGY

David Raben, MD
Dr. Raben is a Professor of Radiation Oncology within the University of Colorado Cancer Center. Dr. Raben has extensive expertise in aerodigestive track malignancies with specific focus in head and neck cancer (HNC). David has developed interests and expertise over the past 20 years in translational radiation oncology with a focus on delivery of precision drugs as well as exploration of molecular biomarkers and targets that will enhance the effects of radiation therapy in HNC. Radiation therapy is rapidly evolving from a technical standpoint with the use of image guided intensity modulated radiation therapy and our group has been one of the leaders in implementing innovative delivery approaches. David currently serves as the Developmental Therapeutics co-Chair at the NRG to initiate and implement Phase I trials with radiation and novel drugs. From a research perspective at Colorado, the Raben lab is currently focused on the heavy smoker patients who have resistant cancers and high levels of DNA repair capabilities in an effort to offer approaches that will inhibit DNA repair along with blocking growth factor signaling. Our laboratory efforts have demonstrated the effectiveness of this type of approach in vitro and are currently studying which biomarkers might predict response to DNA repair inhibitors. Clinical trials are currently being conducted that incorporate agents such as oral DNA PARP inhibitors with growth factor inhibitors in a dual biologic approach to determine if this is the most effective approach for heavy smokers when combined with intensity modulated radiation. New avenues of exploration include the use of immune-modulation agents with radiation for HNC as well as exploring radioprotective strategies with anti-TGFβ agents and metalloporphyrins.
20

 RHEUMATOLOGY

Susan Boackle, MD
Dr. Susan Boackle is Associate Professor of Medicine and Immunology at the University of Colorado School of Medicine. Susan’s clinical and research interests focus on systemic lupus erythematosus.  Lupus is an autoimmune disease that is marked by episodes of increased disease activity called flares, during which antibodies to double stranded (ds) DNA go up, complement levels go down, and inflammation occurs in the body, causing cumulative damage to vital organs over time. The Boackle laboratory has found that a specific change in the sequence of a complement receptor gene expressed in B cells reduces the chances that a person will get lupus. Interestingly, this change specifically appears to protect them from making antibodies to dsDNA. The goal of Dr. Boackle’s research is to develop a new treatment for lupus that mimics the effects of this sequence change. If this treatment is effective, it will stop the production of anti-dsDNA antibodies.  As a result, it will decrease the likelihood that a person with lupus will have another flare of their lupus and reduce the chances that a person who is at risk for lupus will develop the disease.  It also holds promise for other autoimmune diseases in which B cells play a role in disease pathogenesis, such as rheumatoid arthritis, multiple sclerosis, and diabetes mellitus.

Liron Caplan, MD, PhD
Dr. Caplan is the section chief for rheumatology at the Denver Veterans Affairs Medical Center (DVAMC). Liron engages in clinically-oriented epidemiologic and health service research within the fields of pharmacoepidemiology and auto-immunity/rheumatology.  Areas of interest include retrospective analysis of databases to understand long-term medication adverse drug reactions, interventions to optimize medication use, as well as construction and maintenance of patient registries.  Dr. Caplan is Director of the Spondyloarthritis program at the University of Colorado and DVAMC, and has worked with the Program to Understand the Longterm Outcomes in SpondyloARthritis (PULSAR) registry, Veterans Affairs Rheumatoid Arthritis registry, and National Data Bank for Rheumatic Diseases, among others.

Kevin D. Deane, MD, PhD
Dr. Deane is an Associate Professor of Medicine in the Division of Rheumatology/Department of Medicine. His research focused on the natural history of rheumatoid arthritis (RA), and in particular on the ‘preclinical’ period of RA that is characterized by circulating autoantibodies and other markers of immunologic dysfunction that precede the onset of arthritis. More specifically, Kevin’s major translational research efforts are to understand how RA-related autoimmunity may initially be generated at a mucosal site. He has expertise in collection and analyses of biospecimens including saliva, gingival samples, sputum, stool and cervico-vaginal fluid for inflammation, RA-related autoantibodies and microbial factors. In addition, Dr. Deane is the PI on a multi-site NIH-funded clinical trial for the prevention of RA. This trial is entitled ‘StopRA’ (www.stop-ra.org), and entails identifying individuals with serum elevations of RA-related autoantibodies that indicate high risk for onset of arthritis within several years, and treating these individuals with an immunomodulatory therapy (or placebo) to determine if progression to clinically-apparent RA can be halted.


Aryeh Fischer, MD
Dr. Aryeh Fischer is Associate Professor of Medicine at the University of Colorado School of Medicine with a dual appointment in the Divisions of Rheumatology and Pulmonary Sciences as faculty within the Center for Lungs and Breathing. Aryeh’s specific area of clinical and research expertise is within autoimmune associated lung diseases, and autoimmune interstitial lung disease in particular. He has developed clinical expertise with patients referred nationally for evaluation of autoimmune lung disease. Dr. Fischer has served as an invited lecturer on autoimmune and interstitial lung diseases at numerous national and international pulmonary and rheumatology conferences and has published extensively within this domain. He currently serves on the steering committee of four international clinical trials investigating novel therapeutics for autoimmune interstitial lung disease and pulmonary arterial hypertension.

Robert Fuhlbrigge, MD, PhD
Dr. Fuhlbrigge is a Professor of Pediatrics – Rheumatology and is the Section Head for Pediatric Rheumatology at the Children’s Hospital Colorado.

Michael Holers, MD
Dr. Michael Holers is Head, Division of Rheumatology at the University of Colorado Denver. The Holers' research group performs both basic and translational research. A longstanding interest has been to decipher the roles of complement receptors and membrane regulatory proteins in the immune response, with a special emphasis on autoimmune diseases. Complement is a complex system of serum proteins which, upon activation, covalently bind targets (bacteria, viruses, immune complexes) and marks them as foreign. The interaction of complement with B cell receptors also results in substantial enhancement of humoral and cellular immunity. In addition to this role, excessive activation of complement is centrally involved in autoimmunity and the tissue damage that occurs in many inflammatory diseases involving organs such as the kidney. The Holers’ laboratory has developed human and mouse models in which to study these complement related biologic processes and to develop novel complement inhibitors. Candidate therapeutics derived from these studies have been advanced to clinical trials in humans.

With regard to translational research, Dr. Holers is a co-founder of SERA (Studies of the Etiology of Rheumatoid Arthritis), which is focused on understanding the early pathogenesis and natural history of RA. In that regard, we now know that autoimmune diseases such as RA begin years before clinical signs and symptoms are apparent, when at-risk individuals manifest highly predictive autoantibodies in their serum. By studying individuals in this period of time, SERA investigators have made novel findings suggesting that RA is initiated through a process linked to mucosal inflammation. This observation also suggests that additional therapeutic and/or prevention strategies could be considered for individuals in this at-risk but asymptomatic period. It is also relevant to determine how individuals transition from this autoantibody-positive, at-risk period to clinically active disease, and several studies are underway that are related to understanding these questions.

Kristi Kuhn, MD, PhD
Dr. Kuhn is an Assistant Professor in the Division of Rheumatology.  Kristi’s research focuses upon the general hypothesis that impairment of mucosal immune regulation can lead to systemic autoimmune disease. Current work examines how interactions between commensal bacteria and mucosal immune populations educate the peripheral immune response. The identification of the bacterial, T cell, and B cell properties required to establish a functional immune barrier of the intestine, and understanding the downstream immunologic effects with a focus on the development of rheumatologic disease are currently being determined. Dr. Kuhn’s clinical interest is spondyloarthritis with a special emphasis for those with overlapping inflammatory bowel diseases.

Katharine Moore, MD
Dr. Moore is an Assistant Professor in the section of Pediatric Rheumatology. Her specific research interests are in juvenile systemic sclerosis and in the association between antibody profiles, clinical phenotypes and HLA in juvenile systemic sclerosis. Katie also completed additional graduate training in clinical epidemiology and is interested in outcomes research for pediatric autoimmune and autoinflammatory diseases.

Christopher Striebich, MD, PhD
Dr. Striebich is an Associate Professor of Medicine in the Division of Rheumatology and the Director of that division’s Clinical Trials Program. Chris’ interests are in the development and testing of novel immunotherapeutic agents in autoimmune rheumatologic diseases such as systemic lupus erythematous, Sjögren’s syndrome, rheumatoid arthritis, ANCA associated and other forms of systemic vasculitis, inflammatory myositis, psoriatic arthritis and other forms of spondyloarthritis

21

 SURGERY

Ronald Gill, PhD
Dr. Gill is the Scientific Director of the Colorado Center for Transplantation Care, Research and Education (CCTCARE) and a Professor in the Department of Surgery. Ron’s lab has a long-standing interest in both the autoimmune pathogenesis in Type 1 Diabetes (T1D) as well as immunity and tolerance to cellular and solid organ transplants.  Relevant to the HI3 program, Ron’s lab is very interested in continuing the development and pre-clinical testing of therapeutics that promote immune tolerance in both T1D and in transplantation.  Moreover, they are also interested in developing assays for the human immune response to transplants in collaboration with the Transplant Division within the Department of Surgery.


Martin McCarter, MD
Dr. McCarter is a Professor of Surgery specializing in GI Tumor/Endocrinology. Martin’s laboratory is focused on identifying mechanisms of cancer induced immune suppression and identifying ways to interrupt the process. Current projects focus on myeloid derived suppressor cells in melanoma patients; defining, analyzing and targeting these cells to enhance immune-therapeutic interventions. The laboratory is involved in translational science based human clinical trials. In addition, the lab maintains a biobank of human spleen cells and collaborates widely with a variety of investigators utilizing human intestinal tissues.


Dr. Schulick is a Professor and Chair of Surgery at the University of Colorado School of Medicine.

Dan Theodorescu, MD, PhD
Dr. Theodorescu is the Paul Bunn Professor and Director of the NCI designated Comprehensive Cancer Center at the University of Colorado. He is also Professor of Surgery and Pharmacology and Attending Urologic Oncologist. Dan also manages an active translational molecular biology lab focused on identifying the molecular mechanisms leading to bladder and prostate cancer metastasis and their potential applications to patients with these diseases. The Theodorescu team identified the metastasis suppressor gene, RhoGDI2, in human cancer. Expression of this gene has shown to be an independent prognostic marker for disease specific survival in human bladder cancer. Recent mechanistic studies have revealed how this gene affects metastatic phenotype, which resulted in the formulation of a new therapeutic approach to prevent lung metastatic disease. Dan also developed COXEN (CO-eXpressionExtrapolatioN), which is a radical new strategy aimed at personalizing cancer therapy and identifying which new drugs have a high likelihood of being effective in patients based solely on in vitro assays. Proof of principle implementation of these systems has already yielded excellent prediction of patient outcome in several tumor types as well as new candidate compounds for the treatment of human bladder cancer. In addition, recent mass spectrometry based proteomics work has resulted in the discovery of novel urinary biomarkers of bladder and prostate cancer which have been validated in clinical trial and offer the potential for diagnosis and therapy guidance.

Yuwen Zhu, PhD
Dr. Zhu is an Assistant Professor of Surgery, and his research interest is to dissect the molecular hardwires through which tumor cells communicate with immune cells, particularly T lymphocytes. Yuwen’s current research focus is to identify and characterize novel immune checkpoints that shape the tumor microenvironment. The ultimate goal is to translate laboratory findings into the development of new therapeutic options for cancer.

22