Faculty in the Human Immunology and Immunotherapy Initiative have expertise in a wide range of areas relevant to basic and/or translational research in the field of immunology. A brief description of their expertise, research programs, and publications can be found by clicking on the individual member names below.Susan Boackle, MD,
Division of Rheumatology, DOM
James DeGregori, PhD,
Department of Biochemistry
Dr. DeGregori’s 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.
Ronald Gill, PhD,
Dr. Gill’s group 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.
Lia Gore, MD,
Head of Hematology Oncology CHCO
Dr. Gore’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.
Michael Holers, MD,
Head of Rheumatology, DOM
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.
Elena Hsieh, MD,
Department of Pediatrics, Department of Immunology & Microbiology
The goal of the research in Dr. Hsieh’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.
Wells Messersmith, MD,
Head of Medical Oncology, DOM
Dr. Wells 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.
Roberta Pelanda, PhD,
Department of Immunology & Microbiology
Dr. Pelanda, a Professor in the Department of Immunology and Microbiology, is the Director of the Networking and Preclinical Model core facility in 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.
Jill Slansky, PhD,
Department of Immunology & Microbiology
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.