Massachusetts General Hospital | Cancer Center

Nabeel M. Bardeesy, PhD
Associate Professor of Medicine
Harvard Medical School

Assistant Geneticist
Center for Cancer Research

Research Summary

Pancreatic cancer and biliary cancer are among the most lethal types of human cancers.  The Bardeesy laboratory has developed a series of genetically engineered mouse models to define the role of key gene mutations in driving these cancer types. Current projects focus on defining roles for cancer genes in controlling the way cells modulate their growth and utilize energy in response to available nutrients, and on identifying master regulators that promote cancer cells to become more primitive and to metastasize. These efforts point to potential new targets for anticancer drugs.

Nabeel M. Bardeesy, PhD
Principal InvestigatorGroup Members

Postdocs:

• Alexandros (Alex) Tzatsos, PhD
• Julien Fitament, PhD
• Rushika Perera, PhD
• Supriya (Shoop) Saha, PhD
• Filippos Kottakis, PhD
• Christine Parachoniak, PhD

Technicians:

• Svetlana Stoykova, PhD
• Krishna Sumanth Ghanta
• Julia Nagle

Reasearch Projects

The Bardeesy lab focuses on defining the pathways driving the pathogenesis of pancreatic cancer and, in more recent efforts, of biliary cancer. Our lab has developed a series of genetically engineered mouse models that have elucidated the functional interactions of major gene mutations associated with these diseases in humans. Specifically, we have characterized the roles of key cancer genes in the control of cellular differentiation states and in metabolic regulation.

Lkb1 in regulation of metabolism and stem cell quiescence
The Lkb1 tumor suppressor encodes a serine-threonine kinase mutationally inactivated in a subset of pancreatic and biliary cancers. The best-defined functions of Lkb1 are to suppress cell growth and to reprogram metabolic pathways in response to energy stress conditions. Our lab recently showed that Lkb1 is critically required for the function of hematopoetic stem cells (HSCs). HSCs are normally largely quiescent but need to be able to rapidly convert to a highly proliferative state. We showed that Lkb1 is essential for maintaining quiescence of these cells and for ensuring appropriate energy utilization. The laboratory is currently defining the contribution of this program to Lkb1-mediated suppression of epithelial cancers.

Transcriptional reprogramming in pancreatic cancer
An important area of current focus in our lab is to elucidate the epigenetic regulators of pancreatic cancer, with particular attention paid to factors that subvert normal differentiation pathways and that reprogram cancer cell metabolism. As part of these efforts, we defined the tumorigenic role of a number of chromatin-modifying enzymes that are deregulated in pancreatic cancer progression, KDM2B. This histone demethylase is a major regulator both of polycomb repressor complexes that override cancer cell differentiation states and of a distinct program controlling metabolic homeostasis.

Mouse models of biliary cancer
Although biliary cancers are highly aggressive and increasing in incidence, their pathogenesis remains poorly understood. Recent genetic studies have identified multiple recurrent mutations in biliary cancers and have indicated considerable genetic heterogeneity between individual tumors. A key limitation in the field includes a paucity of experimental systems with which to define the contributions of the lesions to biliary cancer progression. We have established a series of genetically engineered mouse models that incorporate combinations of the major mutations found in the human disease. In addition, our ongoing efforts include the development of a human biliary cancer cell line bank for the use of genetic and small-molecule screening in genetically defined subtypes of this cancer.

Control of liver progenitor cells and biliary cancer development
The Hippo pathway is a conserved regulator of organ size. Our lab has shown that this pathway is central for controlling the quiescence of liver progenitor cells, and that its loss leads to massive liver overgrowth and development of both major types of liver cancer (hepatocellular carcinoma and biliary). The lab is studying the circuitry of the Hippo pathway in liver progenitor cells and the key mediators of tumorigenesis downstream of this pathway.

Research Positions at the Bardeesy Laboratory

Research Technician Position at Massachusetts General Hospital

Background and Job Description:
The Bardeesy Lab of Massachusetts General Hospital Cancer Center at Harvard Medical School is accepting applications for a Research Technician position. The laboratory’s focus is on the molecular mechanisms of Pancreatic Cancer and Cholangiocarcinoma.  Specifically, the lab studies how specific gene mutations govern cancer initiation and progression.  The lab has developed a series of engineered mouse models of pancreatic cancer and cholangiocarcinoma to elucidate these questions in a genetically defined setting in vivo. Complementary in vitro biochemical systems will also be employed for refined studies of oncogenic signaling pathways.
Dr. Bardeesy seeks highly motivated candidates who enjoy conducting research and involving themselves in the intellectual life of the laboratory.  He or she will have the opportunity to become involved with all the steps of research being completed by the group, which will lead to numerous publications. Investigators in our laboratory will present at regular laboratory meetings and will be encouraged to attend talks conducted by scientists visiting the Harvard Medical School campus.  The experience gained in the lab will useful for pursuing a career as a researcher or physician.  Previous investigators holding such positions have had success in gaining acceptance to top graduate or medical schools.  Salary is competitive with other institutions and affords comfortable living in the Boston/Cambridge area.  

Job Requirements:
College background in biology, molecular biology, or biochemistry with research experience is preferred. The ideal candidate will be detail-oriented, organized, and able to work independently as well as part of a team in a challenging environment. Excellent communication and organizational skills are necessary.  


Please submit your CV, a brief letter of intent, and a list of 3 references to nelbardeesy@partners.org by April 21st, although submitting before the deadline is advantageous.  Interviews will be scheduled within a few weeks of receiving the application.  Recent college graduates are encouraged to apply.

Postdoctoral Position - Bardeesy Lab

A Postdoctoral Research Fellow position is available to study molecular pathways in the pathogenesis of pancreatic and liver cancer, focusing regulators of cell metabolism and epigenetics.  The candidate is expected to have a PhD in the biological sciences, and be highly motivated with expertise in basic molecular biology and biochemical techniques. The Fellow will have simultaneous academic appointments at the Massachusetts General Hospital and Harvard Medical School.  Studies will involve the use of a number of genetic and biochemical approaches, including genetically engineered mouse models, primary epithelial cell systems, genome-wide analyses, and in vitro genetic screens to study the interplay of epigenetics and metabolism governing cancer initiation and progression.  The position provides a rich intellectual environment within a group of young investigators at the MGH Cancer Center and Center for Regenerative Medicine, with full integration into the large research communities of the Massachusetts General Hospital and Harvard.

Please email a brief cover letter and CV to:

Nabeel Bardeesy, PhD
Massachusetts General Hospital Cancer Center
Harvard Medical School
CPZN 4216
185 Cambridge St.
Boston, MA 02114

nelbardeesy@partners.org

Publications

View a list of publications by researchers at the Bardeesy Laboratory.

Bardeesy Laboratory

Phone: 617-643-2579
Email: nelbardeesy@partners.org