Heads of Laboratories
Senior Attending Physician
Albert Resnick, M.D., Assistant Professor
Laboratory of Molecular Metabolism
Obesity has been estimated to threaten the health of more than 600 million people worldwide and more than one-third of the U.S. population. As a physician-scientist focusing on obesity and metabolic disease, Cohen investigates the molecular origins of metabolic dysfunction related to obesity with the ultimate goal of developing therapies to break the link between them.
Obesity can bring with it myriad serious and even potentially fatal health problems, including cardiovascular disease, type 2 diabetes, and cancer. But these conditions and the timing of their onset are not universal; they develop much later for some patients than others, and some escape almost entirely. A number of reasons—genetics, diet, physical activity, and type of fat—contribute to this variability. Cohen focuses on understanding the molecular underpinnings of obesity-related diseases.
Epidemiological studies have shown visceral adipose tissue, stored around the abdomen, increases risk for illness and death. Meanwhile, subcutaneous adipose deposits around the hips and buttocks do not raise these risks and may even be protective. Evidence suggests the type of adipocytes within these two tissues is responsible for the dichotomy.
In visceral fat, white adipocytes warehouse triglycerides in large droplets. In obesity, this tissue is marked by inflammation and an increased accumulation of immune cells. However, other types of adipocytes may have neutral or even beneficial effects. Brown adipocytes can defend body temperature by converting the chemical energy in glucose and triglycerides into heat and may also make significant contributions to adult metabolism. Likewise, a third type, beige adipocytes, can dissipate energy just like brown adipocytes when activated by cold or certain hormones. In rodents, beige adipocytes occur in clusters surrounded by white adipocytes in subcutaneous fat, suggesting the reason for the neutral to beneficial effects of that tissue. The location and physiological role of beige adipocytes, which are also present in humans, is not yet fully defined.
Using animal and cellular models and translational approaches in humans, Cohen investigates the transcriptional basis for the harmful and health-protecting effects of fat deposits and the adipocytes they contain. Ultimately, he hopes to develop ways to engineer healthier fat by manipulating the regulation of traits associated with different types of adipocytes.
As a postdoc, Cohen identified a promising target for this approach, PRDM16, which binds in a complex with other proteins to regulate gene expression. Cohen and his colleagues found PRDM16 acts as a molecular switch that determines some of the key functional differences between visceral and subcutaneous fat. It does so by activating beige adipocytes, prompting them to burn calories rather than store them. When they knocked out the PRDM16 gene in mice, beige adipocytes no longer functioned properly, and the animals developed obesity, insulin resistance, and fatty liver. Meanwhile, their subcutaneous fat came to resemble visceral fat, both on molecular and morphological levels.
Cohen is now investigating whether a lack of PRDM16 produces the negative health effects associated with visceral fat or whether some other regulatory factor is involved. With mouse models developed as part of his work on transcriptional control, Cohen is also studying the interactions between adipocytes and conditions such as hypertension, cardiovascular disease, and cancer.
A.B. in biology, 1996
The Rockefeller University
Weill Cornell Medical College
Residency in internal medicine, 2004–2007
Columbia University Medical Center
Fellowship in cardiovascular medicine, 2007–2011
Brigham and Women’s Hospital
Dana Farber Cancer Institute and Harvard Medical School, 2009–2014
Assistant Professor, 2015–
The Rockefeller University
Senior Attending Physician, 2015–
The Rockefeller University Hospital
Assistant Attending Physician, 2016–
Memorial Sloan Kettering Cancer Center
Irma T. Hirschl/Monique Weill-Caulier Trust Research Award, 2015
Human Frontier Science Program Young Investigator Grant, 2016
Sinsheimer Award, 2016
American Diabetes Association Accelerator Award, 2017
American Society of Clinical Investigation Young Physician-Scientist Award, 2017
Chi, J. et al. Three-dimensional adipose tissue imaging reveals regional variation in beige fat biogenesis and PRDM16-dependent sympathetic neurite density. Cell Metab. 27, 226–236 (2018).
Chi, J. and Cohen, P. The multifaceted roles of PRDM16: adipose biology and beyond. Trends Endocrinol. Metab. 27, 11–23 (2016).
Cohen, P. et al. Ablation of PRDM16 and beige adipose causes metabolic dysfunction and a subcutaneous to visceral fat switch. Cell 156, 304–316 (2014).
Khandekar, M.J. et al. Molecular mechanisms of cancer development in obesity. Nat. Rev. Cancer 11, 886–895 (2011).
Cohen, P. et al. Role for stearoyl-CoA desaturase-1 in leptin-mediated weight loss. Science 297, 240–243 (2002).