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Christopher A. J. Roman, PhD

Associate Professor and Chairman of Cell Biology
Associate Professor of Medicine

Academic Background

  • B.A. Biochemistry, Harvard University ('84)
  • Ph.D. Biological Chemistry, University of California, Los Angeles ('91)
  • Post-Doctoral Fellowships: The Rockefeller University (1992-1994); the Massachusetts Institute of Technology (1994-1998)

Awards and Honors

  • Outstanding Educator in the Foundations of Medicine (2018)
  • Excellence in Mentoring Award from the Office of Diversity in Education and Research (2018)
  • LGBTQ+ Advocacy Award (2024)
  • The Henry Kunkel Society (since 2010)
  • SUNY Chancellor's Award for Excellence in Faculty Service (2008)
  • Lupus Research Institute: Novel Research Project Award (2006)

Research Overview

My scientific research reflects a career-long fascination with the unique molecular & cellular biology and genetics of B lymphocytes, key mediators of adaptive natural and vaccine immunity.  T and B lymphocytes are white blood cells critical for host defense against microbial diseases and cancer. During their development, they construct the genes encoding antigen binding molecules known as T cell receptors and immunoglobulins, respectively, resulting in a lymphocyte population with a vast repertoire of diverse target antigen specificities. This repertoire is anticipatory in that it exists pre-emptively before infection, having ready among its ranks some lymphocyte clones that by chance happen to recognize molecules expressed by a future pathogen.  Only those lymphocyte clones specific for the pathogen will respond.  Among those, antigen-specific B cells mobilize to secrete immunoglobulin in the soluble effector form known as antibody, which can inactivate and facilitate the destruction of the target.

Lymphocytes that recognize self-molecules naturally arise during development alongside ones that are not self-reactive.  It is typically only the B lymphocytes that express non-self-reactive immunoglobulins that are allowed to mature and take up residence in the body as part of that "pre-emptive" repertoire.  The main research question we focus on is how self-reactive (autoreactive) B lymphocytes are vetted and then either regulated or eliminated as part of establishing immunological “tolerance” to self. The goal is that the research will lead to a better understanding of the underlying causes of major health challenges caused by defects in B lymphocyte development and regulation, such as autoimmune and inflammatory diseases like systemic lupus erythematosus (SLE), that will inform new treatment strategies. Key research technologies and strategies we employ to study gene function are transgenic and knock-out mouse models, primary human and mouse cell culture systems, flow cytometry, and immunohistochemistry. We also collaborate with clinical divisions in Medicine such as Rheumatology and Allergy/Immunology among others.

Background

Early career discoveries on B lymphocyte development included the identification of genes encoding immunoglobulin enhancer binding proteins (refs. 1, 2), demonstrating how immunoglobulin components of the B cell and pre-B cell receptors regulate B cell development (refs. 3, 4), and elucidating the mechanism of action of the VDJ recombinase component Rag1, one of the essential molecules required for the genetic assembly of the genes encoding antigen receptors of B and T cells (refs. 5, 6).

Current Research

The Mitf family of transcription factors in the immune response and in autoimmune disease.

One major focus of my research nowadays is to elucidate how the microphthalmia transcription factor (Mitf) and its close relatives TFE3 and TFEB participate in T and B cell function. Mitf is well known as a master transcriptional regulator of the development of melanocytes, mast cells, and - in conjunction with TFE3 – osteoclasts.  Our prior research on TFEB and TFE3 showed a critical role in the expression of CD40L, a molecule expressed by activated helper T cells required to support B cell activation and humoral immunity (ref. 7).  More recent research of ours on Mitf has shown a critical role in B cell tolerance by enforcing the elimination of self-reactive B cells and regulating B cell activation and homeostasis (Frontiers in Immunology, 2024; ref 8). In ongoing collaborative studies, we are continuing to identify and validate other molecules that are targets of, or otherwise interact with Mitf, TFE3 and TFEB that strongly impact B and T lymphocyte biology, and to clarify the underlying molecular mechanisms by which these transcription factors execute their critical functions that control autoreactive lymphocytes and prevent autoimmune disease.

SMS2 as a key regulator of B cell tolerance in the Germinal Center.

The other area of exciting research on B cell tolerance I contribute to collaborative work led by Dr. Chongmin Huan, which focuses on the lipid biosynthetic enzyme sphingomyelin synthase 2 (SMS2).  We discovered it has an essential role in B cell tolerance and preventing lupus autoimmunity by eliminating self-reactive B lymphocytes that spontaneously emerge in the germinal center (ref. 9).  Current work explores how this pathway might be impaired in human lupus and how it can be targeted to treat it.

References

  1. Roman, C., J. Platero, J. Shuman, and K. Calame. (1990) "Ig/EBP-1, a Ubiquitously Expressed Immunoglobulin Enhancer Binding Protein that is Similar to C/EBP and Heterodimerizes with C/EBP." Genes Devel 4:1404-1416
  2. Roman, C., L. Cohn, and K. Calame. (1991) "Creation of a Transdominant Negative form of Transcription factor mTFE3 by Differential Splicing." Science 254:94-97
  3. Spanopoulou, E., C. Roman, L. Corcoran, M. Schlissel, D. Silver, D. Nemazee, M. Nussensweig, S. Shinton, R. Hardy, and D. Baltimore. (1994). "Functional Immunoglobulin Transgenes Guide Ordered B-Cell Differentiation in RAG-1 Deficient Mice." Genes Devel. 8:1030-1042
  4. Guloglu, F. B., and Roman, C.A.J. (2006) Precursor B cell receptor Signaling Can Be Uncoupled from Surface Expression. J Immunol. Jun 1;176(11):6862-72
  5. Roman, C.,and D. Baltimore. (1996). "Genetic Evidence that the RAG1 Protein Directly Participates in V(D)J Recombination through Substrate Recognition." Proc. Natl. Acad. Sci.USA 93:2333-2338
  6. Roman, C.A., S. R. Cherry, and D. Baltimore. (1997) "Complementation of V(D)J Recombination Deficiency in RAG-1-/-B-Cells Reveals the Requirement of Novel Cysteine Elements in the N-terminus of RAG-1." Immunity 7: 13-24
  7. Huan C, Kelly ML, Steele R, Shapira I, Gottesman SR, Roman C A. (2006). Transcription factor TFE3 and TFEB are critical for CD40 ligand expression and thymus-dependent humoral immunity. Nat Immunol. Oct;7(10):1082-1091.
  8. Amarnani, A, Lopez-Ocasio M, Dilshat R, Anumukonda K, Davila J, Malakhov N, Huan C, Magnusdottir E, Steingrimsson E, Roman CA. Mitf regulates gene expression networks implicated in B cell homeostasis, germinal center responses, and tolerance. Front. Immunol. 2024 Feb 19; 15: 1339325
  9. Ou P, Stanek A, Huan Z,  Roman CA, Huan C.. SMS2 deficiency impairs PKCδ-regulated B cell tolerance in the germinal center. Cell Reports. 2021 Aug 31;36(9):109624.

Teaching

College of Medicine

Foundations

  • Unit 3- Basis of Disease II: Infection and Host Defense

Unit Director; Rheumatology Subunit co-director, PBL
facilitator, lecturer.

  • Unit 2 - Basis of Disease I: Molecules to Cells Immunology Immunology Subunit director, PBL Facilitator; lecturer.

Pathways

School of Graduate Studies

  • Program in Molecular and Cellular Biology
    Graduate Student supervisor and thesis committee member
    MCBI and II contributing faculty

Service

Current

Former

  • Interim Institutional Official
  • Interim Chair, Cell Biology
  • Executive Committee of the College of Medicine (member)
  • Chair, Cancer Scientific Review Committee
  • Faculty research advisor for residency fellowship in Hematology/Oncology
  • Financial Conflict of Interest Committee (Chair and member)
  • Advisory Committee on Research (ACOR; member; Research Subcommittee)
  • IACUC (member)
  • CAPQ (Chair and member)
  • Executive Committee of the School of Graduate Studies (member)
  • Director, Transgenic Mouse Facility (`closed)

Scientific Publications

Full PubMed bibliography of scientific publications

Abstracts and Presentations in Medical Education and Health Equity

  1. Health Equity Advocacy and Leadership (HEAL): A student-initiated educational pathway that empowers medical students to address health disparities and improve patient outcomes and community health. Ahmed, A. Diggs, C. Roman, C. Boutin-Foster. NEGEA 2018 Emerging Issues in Med Education.
  2. Knocking Down Barriers to Health Equity – Using TBL to Integrate Structural Competency with Biomedical Sciences.Wajiha Kazmi Kelsey Sklar, Andrea Martinez, Alexandra Belzie, Aaron Kuang,
    Latia Skerving, Christopher Roman, PhD. The Generalists in Medical Education 42nd Annual Conference: Working Towards Collaboration, Adaptation, and Innovation.  Nov 2021
  3. Applying a Structural Competency Lens to Teach Medical Students about the Social Determinants of Health.Alexandra Greenberg, Kelsey Sklar, Srishty Amarnani, Justin Ingram, Carla Boutin-Foster, MD, MS, Robin Ovitsh, Cameron Page, Christopher Roman. Poster at 2021 Gold Virtual Humanism Conference: Humanism and Healing Conference: Structural Racism and its Impact on Medicine, May 6-8, 2021 Poster at 2021 Clinical Climate Change 3rd Annual Conference, New York, NY, January 2021

 

Recent graduates

Milena Rodriquez, MD/PhD(2023) - Rheumatologist; ECRIP scholar
Nanda Lahiri, PhD(2020) - Principal Scientist in Clinical Immunology and Biomarker Assessment 
Abhimanyu Amarnani, MD/PhD (2018/2020) - Rheumatology Research Resident and Fellow at NYU Langone

 

Department Links

Cell Biology

College of Medicine