Since 1993, David Sherr’s laboratory has conducted research on how common environmental pollutants, such as dioxins, polycyclic aromatic hydrocarbons and PCBs, adversely affect the growth and behavior of several different types of normal and malignant cells. In previous work, the Sherr laboratory studied how environmental chemicals affect the development of the immune system. In specific, his laboratory demonstrated that aromatic hydrocarbons (generated by the combuston of any carbon source) compromise the function of bone marrow cells required for the development of antibody-forming cells. These cells are critical for immune protection against viruses and bacteria. This work had its orignis in Dr. Sherr’s graduate studies on the ontogeny of lymphocyte development.
More recently, Dr. Sherr’s laboratory has focused on the molecular mechanisms that initiate and maintain breast cancer and on the effects of environmental chemicals on these processes. The laboratory has shown that a cellular protein receptor, referred to as the aryl hydrocarbon receptor (AhR), plays an important role in the initiation and progression of human breast cancer. The results explain, in part, the association between environmental chemical exposure and breast cancer risk. Perhaps most importantly, these studies demonstrate that the AhR drives human breast cancer cells to invade and, presumably, metastasize even in the absence of environmental chemicals. These observations have led to the development of AhR inhibitors which block AhR activity and prevent tumor cells from invading. One immediate goal of the laboratory, therefore, is the development of potent AhR inhibitors as novel, targeted therapeutics to be used for treatment of all breast cancers but especially for treatment of “triple negative” or chemotherapy-resistant breast cancers. Interestingly, preliminary studies suggest that these AhR inhibitors could be useful for treatment of several other cancer cell types.
A new area of study in Dr. Sherr’s laboratory is the analysis of the role of the AhR in blood cell development. These studies are important from both an environmental science and medical science point of view. Studies performed to date suggest that the AhR plays an important roll in the normal development of blood cells. The results suggest the intriguing possibility that common environmental pollutants can alter normal blood cell development by interfering with AhR signaling.
Dr. Sherr came to BUSPH from the faculty of Harvard Medical School, where he had earlier been a postdoctoral fellow in the department of Nobel Laureate Baruj Benacerraf. The Sherr Laboratory is funded by research grants from the National Institute of Environmental Health Sciences, the NIH Superfund Basic Research Program, and the Art BeCAUSE breast cancer foundation. Dr. Sherr is the Director of the Boston University Immunology Training Program, and a member of the Amyloid Treatment Research Program, the BU Cancer Center, the Hematology/Oncology Training Program, and the BU Hormone-dependent Cancer Center. He has trained 21 postdoctoral (M.D. or Ph.D.) and 11 predoctoral (M.D. and/or Ph.D.) fellows.
- Graduate Faculty (Primary Mentor of Grad Students), Boston University School of Medicine, Division of Graduate Medical Sciences
- Professor, Pathology & Laboratory Medicine, Boston University School of Medicine
- Director, Superfund Research Program , Boston University
- Director, Immunology Training Program, Boston University
- Cornell University, PhD
- Brandeis University, BA
- Published on 3/23/2018
Leung A, Zulick E, Skvir N, Vanuytsel K, Morrison TA, Naing ZH, Wang Z, Dai Y, Chui DHK, Steinberg MH, Sherr DH, Murphy GJ. Notch and Aryl Hydrocarbon Receptor Signaling Impact Definitive Hematopoiesis from Human Pluripotent Stem Cells. Stem Cells. 2018 Mar 23. PMID: 29569827.
- Published on 3/21/2018
Rothhammer V, Borucki DM, Kenison JE, Hewson P, Wang Z, Bakshi R, Sherr DH, Quintana FJ. Detection of aryl hydrocarbon receptor agonists in human samples. Sci Rep. 2018 Mar 21; 8(1):4970. PMID: 29563571.
- Published on 11/22/2017
Shashar M, Belghasem ME, Matsuura S, Walker J, Richards S, Alousi F, Rijal K, Kolachalama VB, Balcells M, Odagi M, Nagasawa K, Henderson JM, Gautam A, Rushmore R, Francis J, Kirchhofer D, Kolandaivelu K, Sherr DH, Edelman ER, Ravid K, Chitalia VC. Targeting STUB1-tissue factor axis normalizes hyperthrombotic uremic phenotype without increasing bleeding risk. Sci Transl Med. 2017 Nov 22; 9(417). PMID: 29167396.
- Published on 5/5/2017
Ash PEA, Stanford EA, Al Abdulatif A, Ramirez-Cardenas A, Ballance HI, Boudeau S, Jeh A, Murithi JM, Tripodis Y, Murphy GJ, Sherr DH, Wolozin B. Dioxins and related environmental contaminants increase TDP-43 levels. Mol Neurodegener. 2017 05 05; 12(1):35. PMID: 28476168.
- Published on 3/23/2017
Mulas F, Li A, Sherr DH, Monti S. Network-based analysis of transcriptional profiles from chemical perturbations experiments. BMC Bioinformatics. 2017 Mar 23; 18(Suppl 5):130. PMID: 28361664.
- Published on 1/1/2017
Wang Z, Monti S, Sherr DH. The diverse and important contributions of the AHR to cancer and cancer immunity. 2017; 2:102-107.
- Published on 8/29/2016
Novikov O, Wang Z, Stanford EA, Parks AJ, Ramirez-Cardenas A, Landesman E, Laklouk I, Sarita-Reyes C, Gusenleitner D, Li A, Monti S, Manteiga S, Lee K, Sherr DH. An Aryl Hydrocarbon Receptor-Mediated Amplification Loop That Enforces Cell Migration in ER-/PR-/Her2- Human Breast Cancer Cells. Mol Pharmacol. 2016 Nov; 90(5):674-688. PMID: 27573671.
- Published on 7/30/2016
Chen HR, Sherr DH, Hu Z, DeLisi C. A network based approach to drug repositioning identifies plausible candidates for breast cancer and prostate cancer. BMC Med Genomics. 2016 Jul 30; 9(1):51. PMID: 27475327.
- Published on 4/29/2016
Stanford EA, Ramirez-Cardenas A, Wang Z, Novikov O, Alamoud K, Koutrakis P, Mizgerd JP, Genco CA, Kukuruzinska M, Monti S, Bais MV, Sherr DH. Role for the Aryl Hydrocarbon Receptor and Diverse Ligands in Oral Squamous Cell Carcinoma Migration and Tumorigenesis. Mol Cancer Res. 2016 Aug; 14(8):696-706. PMID: 27130942.
- Published on 4/11/2016
Smith BW, Stanford EA, Sherr DH, Murphy GJ. Genome Editing of the CYP1A1 Locus in iPSCs as a Platform to Map AHR Expression throughout Human Development. Stem Cells Int. 2016; 2016:2574152. PMID: 27148368.
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