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Pete Watson, Ph.D.

Associate Professor of Medicine

My work has focused on cardiac and vascular adaptation to both physiological and pathological states. Work in the heart has focused on the crucial distinctions that define physiological growth of the left ventricle, like that seen with exercise, from pathological hypertrophy and subsequent failure in response to hypertension and diabetes. Two distinct regulatory mechanisms have been explored as potential regulators of sex-specific outcomes from cardiac remodeling.  The first involves the sex-specific actions of the transcription factor CREB in the heart.  CREB is important for establishing and maintaining physiological function in both the heart and vasculature, acting to increase resistance to programmed cell death (apoptosis) and balancing energy production to increased energy demands through increases in mitochondrial respiratory capacity.  The second involves the anti-inflammatory cytokine Interleukin-19 (IL-19) which is produced by both cardiac myocytes and cardiac fibroblasts in the heart.  Sex-related differences in levels of expression of this cytokine and its receptors in the heart, and modulation of expression in the heart in response to stimuli for remodeling make this newly discovered cytokine a strong candidate in mediating sex-specific outcomes from cardiac remodeling. 


Heart disease is frequently perceived as a disease which mainly impacts men; however a review of epidemiological studies does not support such a perception. Sexually divergent manifestation of heart failure has been observed in response to specific etiological factors. Heart failure subsequent to myocardial infarction (MI) and hypertension have proven to be particularly deadly for women. Similarly, diabetes has been reported to be a stronger risk factor for heart failure in women than in men with large population studies identifying an 8-fold increase incidence of heart failure in women with diabetes versus a 4-fold increase in men with diabetes. Morbidity and mortality from heart failure also demonstrate significant sexual dimorphism. Women who develop heart failure are more likely to remain symptomatic and to be more functionally limited, experience less 1 year improvement in symptoms, and a greater rate of mortality with 62.4 percent of heart failure deaths since the year 2000 occurring in women.

Thus, while women appear to have a resilient coronary vascular phenotype, they also appear to have a “susceptible” cardiac phenotype which is revealed subsequent to diabetes, hypertension, or MI.

Work in our laboratory has focused on two regulatory molecules expressed by cardiac cells which appear to influence sex-specific differences in the phenotype of the remodeling heart.

For several years, we have studied the impact of the loss of signaling to the transcription factor CREB, which occurs early in the etiology of heart failure in a plethora of rodent models. Our recent studies, utilizing on a transgenic mouse model expressing a phosphorylation-deficient CREB mutant in a heart-specific manner, suggest that CREB dysfunction in the heart exposes mitochondrial and contractile cardiac susceptibilities in the female sex, manifesting prior to puberty. In other words, CREB dysfunction in the context of cardiac remodeling reveals sexually-dimorphic cardiac phenotypes. The focus of the work in my laboratory is to utilize these sex-related mitochondrial and contractile phenotypes to access the molecular underpinnings contributing to the sexually-divergent manifestations of heart failure, and subsequent morbidity and mortality from pathological cardiac remodeling by the sexes.

Recently, studies have been initiated in the laboratory on a newly described anti-inflammatory cytokine IL-19.  Originally thought to be limited in expression to immune cells, recent work in our laboratory has demonstrated that this cytokine (1) is expressed in the heart, (2) is expressed in both cardiac myocytes and fibroblasts, (3) is differentially expressed in the heart by sex, with female hearts showing more robust expression, and (4) is modulated in its content in response to stimuli which lead to remodeling of the heart.  Both isoforms of IL-19 receptors are expressed in the heart, and their relative abundance differs by sex as well.  Preliminary studies indicate that IL-19 stimulation of cultured cardiac fibroblasts alters the expression of proteins essential for remodeling the extracellular matrix in the heart.  This leads to speculation that IL-19 may be essential for cardiac repair in response to injuyry. 

  • Cardiac Failure
  • Exercise
  • Mitochondrial function
  • Diabetes
  • Cytokines
  • Fibrosis

Selected Publications

  1. Estrogenic compounds are not always cardioprotective and can be lethal in males with genetic heart disease.
    Haines CD, Luczak ED, Harvey PA, Barthel KK, Konhilas JP, Watson PA, Stauffer BL, Leinwand LA.
    Endocrinology, 2012 Sep;153(9):4470-9. doi: 10.1210/en.2012-1391. Epub 2012 Jul 9.
  2. Selective class I histone deacetylase inhibition suppresses hypoxia-induced cardiopulmonary remodeling through an antiproliferative mechanism.
    Cavasin MA, Demos-Davies K, Horn TR, Walker LA, Lemon DD, Birdsey N, Weiser-Evans MC, Harral J, Irwin DC, Anwar A, Yeager ME, Li M, Watson PA, Nemenoff RA, Buttrick PM, Stenmark KR, McKinsey TA.
    Circ Res. 2012 Mar 2;110(5):739-48. Epub 2012 Jan 26.
  3. Fatty liver is associated with reduced SIRT3 activity and mitochondrial protein hyperacetylation.
    Kendrick AA, Choudhury M, Rahman SM, McCurdy CE, Friederich M, Van Hove JL, Watson PA, Birdsey N, Bao J, Gius D, Sack MN, Jing E, Kahn CR, Friedman JE, Jonscher KR.
    Biochem J. 2011 Feb 1;433(3):505-14.
  4. Cardiac-specific overexpression of dominant-negative CREB leads to increased mortality and mitochondrial dysfunction in female mice.
    Watson PA, Birdsey N, Huggins GS, Svensson E, Heppe D, Knaub L.
    Am J Physiol Heart Circ Physiol. 2010 Dec;299(6):H2056-68. Epub 2010 Oct 8.
  5. Fatty acids increase glucose uptake and metabolism in C2C12 myoblasts stably transfected with human lipoprotein lipase.
    Capell WH, Schlaepfer IR, Wolfe P, Watson PA, Bessesen DH, Pagliassotti MJ, Eckel RH.
    Am J Physiol Endocrinol Metab. 2010 Oct;299(4):E576-83. Epub 2010 Jul 13.
  6. CREB downregulation in vascular disease: a common response to cardiovascular risk.
    Schauer IE, Knaub LA, Lloyd M, Watson PA, Gliwa C, Lewis KE, Chait A, Klemm DJ, Gunter JM, Bouchard R, McDonald TO, O'Brien KD, Reusch JE.
    Arterioscler Thromb Vasc Biol. 2010 Apr;30(4):733-41. Epub 2010 Feb 11.
  7. Restoration of CREB function is linked to completion and stabilization of adaptive cardiac hypertrophy in response to exercise.
    Watson PA, Reusch JE, McCune SA, Leinwand LA, Luckey SW, Konhilas JP, Brown DA, Chicco AJ, Sparagna GC, Long CS, Moore RL.
    Am J Physiol Heart Circ Physiol. 2007 Jul;293(1):H246-59. Epub 2007 Mar 2.


Graduate Schools
Ph.D., University of Texas Graduate School of Biomedical Sciences (1983)
M.S., Ball State University (1980)

Undergraduate School
B.S., University of Notre Dame (1977)

M.S. Hershey Medical Center, The Pennsylvania State University (1983-85)