Since 1993, Dr. Sherr's laboratory has conducted research on how common environmental pollutants, such as dioxins, polycyclic aromatic hydrocarbons (PAHs) and PCBs, suppress the immune system and induce cancer. This work has focused on molecular signals initiated by the aryl hydrocarbon receptor (AhR), a cell protein that famously is activated by a variety of common environmental chemicals. Reasoning that evolution did not select out the AhR to recognize human pollution, the Sherr lab began using environmental chemicals that activate the AhR to learn what the true function of this curious protein is. The Sherr lab was the first to demonstrate dramatically high levels of the AhR in breast cancer, an observation that would eventually be extended to cancers of the oral cavity, brain, and lung. The lab showed that, while the AhR in these cancers could be hyper-activated with environmental chemicals, the receptor was already in the “on” position, even in the absence of such chemicals. Using novel AhR inhibitors that the laboratory developed, and state-of-the-art molecular technologies including CRISPR/Cas9 gene editing, the lab demonstrated that pre-cancers and cancers were exploiting this receptor/signaling protein to up-regulate expression of genes that drive cancer invasion, metastasis, and longevity. Specifically, the AhR was shown to enforce the development of cancer stem cells, a small but critical subset of tumor cells that are highly resistant to chemotherapy and radiotherapy and are prone to metastasize.
Again returning to the biologic effects of environmental chemicals, the Sherr lab then began to investigate why environmental chemicals tend to be immunosuppressive, an effect of exposure to these chemicals known to toxicologists for many years. Again, using these chemicals as probes of AhR function in biologic systems, the lab demonstrated that the AhR suppresses otherwise effective cancer-specific immune responses through the up-regulation of “immune checkpoints”, molecules that shut the immune system off. The evolving ability to inhibit these immune checkpoints with specific immune checkpoint inhibitors (PD-L1-targeted drugs) is driving the current excitement around cancer immunotherapy. That environmental chemicals increase immunosuppression through up-regulation of these immune checkpoints not only explains why environmental chemicals suppress immunity (they activate the AhR in suppressive cells of the immune system), but also suggests that some environmental chemicals deliver a double hit, first by pushing benign cells towards becoming aggressive malignancies and then through inhibition of the one biologic system capable of defending against all forms of cancers, i.e., the immune system.
While the Sherr laboratory has historically been oriented towards understanding the biologic effects of environmental chemicals to prevent cancer and to understand the basic molecular mechanisms behind cancer aggression and immunosuppression, it has most recently begun investigating how to detect the changes in cells that precede cancer formation and how to intercept cancer at these inflection points before it develops. To this end, the laboratory is now exploiting its proprietary AhR inhibitors and advanced gene editing techniques to boost anti-cancer immunity and to block transformation of benign cells into malignant cells.
Dr. Sherr came to BUSPH from the faculty of Harvard Medical School, where he had earlier been a postdoctoral fellow with Martin Dorf in the department of Nobel Laureate Baruj Benacerraf. His research has been supported continually by the NIH through the R01, P01, and/or P42 mechanisms since 1987.
He was the founding Director of the BU Flow Cytometry Core, a former Director of the BU Immunology Training Program, and a former Director of the NIH-funded Boston University Superfund Research Program. He is currently a Co-director of the Cancer Interception Group in the BU-BMC Cancer Center and is the Director of the Find The Cause Breast Cancer Foundation Research Consortium. His laboratory is funded by research grants from the National Institute of Environmental Health Sciences and the Find the Cause Breast Cancer Foundation. He has trained 11 undergraduate students, four Masters students, 16 Ph.D. or M.D./Ph.D. students and 24 Postdoctoral Fellows and has won the BU School of Public Health Excellence in Teaching award three times and has been nominated for the Boston University-wide Educator of the Year award 4 times.
- Professor, Pathology & Laboratory Medicine - Boston University School of Medicine
- Member, BU-BMC Cancer Center - Boston University
- Member, Amyloidosis Center - Boston University
- Member, Evans Center for Interdisciplinary Biomedical Research - Boston University
- Member, Genome Science Institute - Boston University
- Director, Superfund Research Program - Boston University
- Director, Immunology Training Program - Boston University
- Graduate Faculty (Primary Mentor of Grad Students) - Boston University School of Medicine, Graduate Medical Sciences
- Cornell University, PhD Field of Study: Microbiology
- Brandeis University, BA Field of Study: Biology
- Published on 1/4/2022
Arinze NV, Yin W, Lotfollahzadeh S, Napoleon MA, Richards S, Walker JA, Belghasem M, Ravid JD, Hassan Kamel M, Whelan SA, Lee N, Siracuse JJ, Anderson S, Farber A, Sherr D, Francis J, Hamburg NM, Rahimi N, Chitalia VC. Tryptophan metabolites suppress the Wnt pathway and promote adverse limb events in chronic kidney disease. J Clin Invest. 2022 01 04; 132(1). PMID: 34752422.
- Published on 5/11/2021
Kenison JE, Wang Z, Yang K, Snyder M, Quintana FJ, Sherr DH. The aryl hydrocarbon receptor suppresses immunity to oral squamous cell carcinoma through immune checkpoint regulation. Proc Natl Acad Sci U S A. 2021 05 11; 118(19). PMID: 33941684.
- Published on 3/8/2021
Koual M, Tomkiewicz C, Guerrera IC, Sherr D, Barouki R, Coumoul X. Aggressiveness and Metastatic Potential of Breast Cancer Cells Co-Cultured with Preadipocytes and Exposed to an Environmental Pollutant Dioxin: An in Vitro and in Vivo Zebrafish Study. Environ Health Perspect. 2021 03; 129(3):37002. PMID: 33683140.
- Published on 12/31/2020
Wang Z, Snyder M, Kenison JE, Yang K, Lara B, Lydell E, Bennani K, Novikov O, Federico A, Monti S, Sherr DH. How the AHR Became Important in Cancer: The Role of Chronically Active AHR in Cancer Aggression. Int J Mol Sci. 2020 Dec 31; 22(1). PMID: 33396563.
- Published on 11/25/2020
Kenison JE, Jhaveri A, Li Z, Khadse N, Tjon E, Tezza S, Nowakowska D, Plasencia A, Stanton VP, Sherr DH, Quintana FJ. Tolerogenic nanoparticles suppress central nervous system inflammation. Proc Natl Acad Sci U S A. 2020 12 15; 117(50):32017-32028. PMID: 33239445.
- Published on 10/1/2020
Giovannoni F, Bosch I, Polonio CM, Torti MF, Wheeler MA, Li Z, Romorini L, Rodriguez Varela MS, Rothhammer V, Barroso A, Tjon EC, Sanmarco LM, Takenaka MC, Modaresi SMS, Gutiérrez-Vázquez C, Zanluqui NG, Dos Santos NB, Munhoz CD, Wang Z, Damonte EB, Sherr D, Gehrke L, Peron JPS, Garcia CC, Quintana FJ. Author Correction: AHR is a Zika virus host factor and a candidate target for antiviral therapy. Nat Neurosci. 2020 Oct; 23(10):1307. PMID: 32778795.
- Published on 7/20/2020
Giovannoni F, Bosch I, Polonio CM, Torti MF, Wheeler MA, Li Z, Romorini L, Rodriguez Varela MS, Rothhammer V, Barroso A, Tjon EC, Sanmarco LM, Takenaka MC, Modaresi SMS, Gutiérrez-Vázquez C, Zanluqui NG, Dos Santos NB, Munhoz CD, Wang Z, Damonte EB, Sherr D, Gehrke L, Peron JPS, Garcia CC, Quintana FJ. AHR is a Zika virus host factor and a candidate target for antiviral therapy. Nat Neurosci. 2020 08; 23(8):939-951. PMID: 32690969.
- Published on 10/30/2019
Walker JA, Richards S, Belghasem ME, Arinze N, Yoo SB, Tashjian JY, Whelan SA, Lee N, Kolachalama VB, Francis J, Ravid K, Sherr D, Chitalia VC. Temporal and tissue-specific activation of aryl hydrocarbon receptor in discrete mouse models of kidney disease. Kidney Int. 2020 03; 97(3):538-550. PMID: 31932072.
- Published on 9/17/2019
Krishnan S, Ding Y, Saeidi N, Choi M, Sridharan GV, Sherr DH, Yarmush ML, Alaniz RC, Jayaraman A, Lee K. Gut Microbiota-Derived Tryptophan Metabolites Modulate Inflammatory Response in Hepatocytes and Macrophages. Cell Rep. 2019 Sep 17; 28(12):3285. PMID: 31533048.
- Published on 9/1/2019
Takenaka MC, Gabriely G, Rothhammer V, Mascanfroni ID, Wheeler MA, Chao CC, Gutiérrez-Vázquez C, Kenison J, Tjon EC, Barroso A, Vandeventer T, de Lima KA, Rothweiler S, Mayo L, Ghannam S, Zandee S, Healy L, Sherr D, Farez MF, Prat A, Antel J, Reardon DA, Zhang H, Robson SC, Getz G, Weiner HL, Quintana FJ. Author Correction: Control of tumor-associated macrophages and T cells in glioblastoma via AHR and CD39. Nat Neurosci. 2019 Sep; 22(9):1533. PMID: 31197266.
News & In the Media
- Published on September 8, 2020
- Published on October 24, 2019
- Published on June 5, 2019
- Published on April 9, 2019
- Published on May 16, 2018
- Published on November 26, 2017
- Published on July 11, 2016
- Published on April 15, 2015
- Published on February 19, 2015
- Published on May 21, 2014