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Thermogenic Fat

Obesity and Cancer

Inter-Organ Communication

About Our Research

The Cohen Lab is interested in a number of questions that may help explain why obesity increases the risks of deadly co-morbidities:

  • What are the molecular mechanisms underlying the phenotypic identity and plasticity of fat cells?
  • What are the specific phenotypes regulated by distinct fat cells (white, brown, and beige)?
  • How does fat cell phenotype contribute to disease?
  • Can we develop approaches to modulate fat cell phenotype?

Our interdisciplinary team collaborates with a number of labs to investigate adipose biology at the molecular, cellular, and organismal level.

The Cohen Lab is investigating a diverse array of questions related to adipose biology and metabolic disease. Chiefly, the Cohen Lab is concerned with obesity and associated metabolic disorders. Obesity is associated with a spectrum of metabolic diseases, such as hypertension, diabetes, dyslipidemia, and many types of cancer. Together, these contribute to the leading causes of morbidity and mortality worldwide. One in three adults in this country are obese, leading to nationwide health care costs upwards of $100 billion per year. While there appears to be a clear overlap between obesity and the development of metabolic diseases, there also exists an interesting subset of population where obese individuals are metabolically healthy. This begs the question, how does adipose tissue contribute to the development of co-morbidities, and what underlying differences exist to explain why some obese individuals seem to be protected from these effects?

The location where excess fat is stored is strongly correlated with the likelihood of developing metabolic disorders. Obese individuals with increased visceral fat are characterized by low-grade chronic inflammation and are much more likely to develop comorbid conditions, while obese individuals with increased subcutaneous fat are less likely to develop these sequelae. If we probe further, down to the cellular level, we find that there are a variety of types of fat cells which are present in differing compositions across fat depots. White adipocytes store energy in lipid droplets and can contribute to inflammation in the setting of obesity. Brown adipocytes are rich in mitochondria and can dissipate energy through adaptive thermogenesis, with anti-obesity and anti-diabetes effects. There is a third type of fat cell called a beige adipocyte. These cells are embedded within adult white adipose depots and can be activated by cold, sympathetic input, or other stimuli to dissipate energy like brown adipocytes. Recent work has shown that the phenotype of fat cells is regulated by a transcriptional coregulatory protein PRDM16, which when deleted results in an ablation of beige fat and more unhealthy visceral-like fat. We are now focused on further dissecting the key molecular controls governing fat cell phenotype with the ultimate goal of engineering healthier fat.

Adipose Tissue Microenvironment

Co-developed with Marc Tessier-Levine’s lab here at Rockefeller, we adapted the iDISCO whole-tissue clearing protocol to suit the unique optical properties of adipose tissue. We have applied this technique initially to study the interaction between the sympathetic nervous system (SNS) and adipocytes and discovered that, in addition to the well-described regulatory role which SNS fibers exert on adipocytes, adipocytes themselves can also regulate the patterning of SNS in adipose tissue. We are now applying this technique to a range of questions relating to the adipose tissue microenvironment.

Inter-Organ Communication

Since the discovery of leptin, adiponectin, and adipsin in the 1990s, adipose tissue has been appreciated as a key endocrine organ regulating diverse physiological processes. These include feeding behavior, thermogenesis, insulin sensitivity, insulin secretion, angiogenesis, and more. Bioinformatics analyses suggest that as many as 1000 proteins may be secreted from adipocytes. We are interested in studying the secretome of adipose tissue, as well as questions around inter-organ communication more broadly in health and disease. Recently, we have employed bio-orthogonal non-canonical amino acid tagging (BONCAT) to selectively label and enrich for polypeptides secreted by fat. Several projects in the lab are involved in scaling and optimizing this approach for adipose tissue and other organ systems in diverse biological contexts.

Obesity and Cancer

Obesity is a known risk factor for many diseases. Increasingly, obesity is being linked to increased morbidity and mortality in cancer, as well as increased incidence of various cancer types. Obesity has now eclipsed smoking as the leading preventable cause of cancer. However, the mechanistic links between obesity and cancer initiation, progression, and outcome have been understudied. We have recently discovered that adipocyte-derived creatine acts as a fuel for a model of triple-negative breast cancer. We are interested in examining the link between obesity and cancer in other cancer types and whether adipocyte-derived creatine may act as a fuel in other cancer types.

Brown Fat in Humans

In 2009, functional brown fat was identified in adult humans through 18F-FDG-PET/CT scans using radiolabelled glucose. This generated hope for those hoping to employ brown fat biology in the treatment of human metabolic dysfunction. Recently, our lab extended these findings and showed in a retrospective cohort of 53,475 patients who received 18F-FDG-PET/CT scans, patients who had detectable brown fat on their scan had lower odds ratios of a host of factors, including type II diabetes, coronary heart disease, and hypertension. The lab is broadly interested in translational research to understand the role of adipose tissue in health and disease.

 

Our Lab

The Cohen Lab is made up of Ph.D. students, M.D./Ph.D. students, medical students, postdoctoral fellows, visiting scholars, and clinical scholars. We come from a diverse range of backgrounds and are all passionate about our science. Click the photos below to learn more about each of us:

Paul Cohen, M.D., Ph.D.

Paul Cohen is the Albert Resnick, M.D. Assistant Professor at the Rockefeller University. Paul has headed the Laboratory of Molecular Metabolism since 2015. He is also Senior Attending Physician at The Rockefeller University Hospital and Assistant Attending Physician at Memorial Sloan Kettering Cancer Center. Paul completed postdoctoral training at the Dana Farber Cancer Institute, a Fellowship in Cardiovascular Medicine at the Brigham and Women's Hospital, and a residency in internal medicine at Columbia University Medical Center. Prior to that, Paul was a student in the Tri-Institutional M.D./Ph.D. program here at Rockefeller, where he completed Ph.D. research in Jeff Friedman's lab. Paul received his A.B. in Biology from Harvard College.

Jingyi Chi

Jingyi Chi is a Helmsley Graduate Fellow in the Cohen Lab. Jingyi received an undergraduate degree from the University of Wisconsin, Madison. She is interested in understanding how various adipose tissue components interact in response to development, physiological, and pathophysiological stimuli using whole-tissue imaging coupled with molecular and genetic tools.

Chan Hee Choi

Chan Hee Choi is a biomedical fellow in the Tri-Institutional M.D./Ph.D. program with Sloan Kettering, Rockefeller, and Weill Cornell Medical College. He is currently a William Randolph Hearst Scholar. He received his undergraduate degree in Biochemistry from the University of Chicago. Chan Hee is studying the secretome of different types of adipocytes.

Francois Marchildon, Ph.D.

Francois Marchildon is a postdoctoral fellow in the Cohen Lab studying exercise oncology, cancer cachexia, molecular stamina, and sarcopenia. He received his B.A.Sc in Biotechnology from La Cite in Ottawa, Ontario and his Ph.D. in Cellular and Molecular Medicine at the University of Ottawa. In the Cohen Lab, he has been a Helmsley Postdoctoral Fellow and is currently an FRQS postdoctoral fellow. Francois is an opera neophyte.

Aarthi Maganti-Vijaykumar, Ph.D.

Aarthi Maganti-Vijaykumar is a Helmsley Postdoctoral Fellow in the Cohen Lab. She completed her undergraduate B.E. and B.M.S. degrees at the College of Engineering in India. She then completed her Ph.D. at the Indiana University School of Medicine. Aarthi is interested in Obesity and Type II Diabetes.

Will Barr

Will is currently a research assistant in the Cohen Lab and is planning to enter a Ph.D. program in interdisciplinary/systems biology in the next few years. Previously, Will received his B.A. with a triple major in Integrative Sciences, Molecular Biology & Biochemistry, and Science and Technology Studies at Wesleyan University. He conducted undergraduate and master's level research projects spanning molecular biology, bioinformatics, and computational biophysics. Will is interested in applying tools from synthetic biology to understand and identify molecular targets in human disease.

Zeran (Rico) Lin

Zeran is a Ph.D. student in the David Rockefeller Graduate Program. She previously received her B.A. from Cornell University, where she performed undergraduate research in plant biology. Zeran is interested in studying cell-cell interactions in adipose tissue microenvironment and their dynamics under different physiological conditions. She also likes fungi and plants!

Sarah Szwed

Sarah Szwed is a student in the Tri-Institutional M.D./Ph.D. program. She previously received her B.A. with a double-major in Biology and Dance at Barnard College. She then worked as a Research Assistant at the Rockefeller University studying songbird vocal learning and then at the Novartis Institute working in chemical genomics. Sarah also received her M.Sc. in Biology with honors from Heinrich-Heine Universität Düsseldorf.

Kaja Plucinska, Ph.D.

Kaja is currently a postdoctoral fellow in the Cohen Lab beginning a project with a dual-affiliation with Rockefeller and the Center for Basic Metabolic Research at the University of Copenhagen. She was previously a postdoctoral fellow at the University of Aberdeen where she studied the neuronal links between dementia and systemic diabetes. She received her Ph.D. in neuroscience also from the University of Aberdeen. As a neuroscientist with training in adipose biology, Kaja is fascinated by the functions of brown fat beyond thermogenesis, such as secretion of potent circulating factors (BATokines). She is particularly interested in the cross-talk between brown fat and other organs including the brain to regulate homeostatic behaviors, appetite and insulin sensitivity during normal physiology and pathophysiology such as obesity and diabetes. Kaja also loves music, ramen, and playing squash.

Xiaojing Huang, M.D., Ph.D.

Xiaojing Huang is a graduate of the MD-PhD program at Washington University in St. Louis and a resident in Radiation Oncology at Memorial Sloan Kettering Cancer Center. She joined the Cohen Lab to investigate the mechanisms linking obesity to cancer development and progression. She is interested in metabolism, cancer biology, informatics, and rock climbing.

Mascha Koenen, Ph.D.

Dr. Mascha Koenen studied Biology at the Heinrich-Heine University Düsseldorf, Germany, where she worked on the impact of genetic risk factors for obesity and their influence on the development of atherosclerosis during her Master’s thesis. Mascha then moved on to the University of Ulm for her PhD in molecular medicine, investigating the underlying cellular interactions critical for successful steroid therapy of rheumatoid arthritis. After her PhD Mascha relocated to the US to join the Immunobiology Department at Yale University and in 2020 became a postdoctoral associate at the Cohen Lab at Rockefeller University in New York. Mascha is enthusiastic about the interplay of adipocytes and immune cells and their impact on cardiovascular diseases. Outside the lab she loves to explore new restaurants and meet up with friends.

Join the Lab!

We are always interested in hearing from people interested in our work. Please email pcohen[at]rockefeller[dot]edu with any questions

Contact Us

We are located in the Stavros-Niarchos Foundation/David Rockefeller River Campus at The Rockefeller University. Our lab sits on the second floor of the Kravis Research Building overlooking the East River. Rockefeller neighbors Weill Cornell Medical College and Memorial Sloan Kettering Cancer Center.