
Mark R. Boothby, M.D., Ph.D.
- Professor of Pathology, Microbiology and Immunology
- Professor of Medicine
Phone
AA-4214B Medical Center North
Nashville, TN 37232-2363
Mark R. Boothby, M.D., Ph.D.
- Professor of Pathology, Microbiology and Immunology
- Professor of Medicine
615-343-1699
mark.boothby@vumc.org
AA-4214B Medical Center North
Nashville, TN 37232-2363
Research Program
Departments/Affiliations
Profile
Education
Research Emphasis
Signaling and gene regulation mechanisms in immune system hematopoietic cells, especially those of B and T lymphoid lineages.
Lymphoid lineage cells are the most central means of regulating characteristics of immunity and auto-immunity, and they also are vital in the inflammation and pathophysiology of most of the main disease burden in the US (atherosclerotic vascular disease with heart attacks and strokes, obesity, diabetes, and cancer), The lab seeks to identify new signal transduction, transcription, and chromatin or epigenetic ways in which lymphoid lineage cells are regulated, with active investigations in immunity, auto-immunity (autoimmunity) and the ways in which sustained antibody responses are evoked since antibody levels are crucial in the efficacy of vaccines and are key components in a variety of autoimmune diseases. The most recent focus is a multi-disciplinary approach stemming from a need to understand (1) at a micro-anatomic level what is the actual constitution of nutrient micro-environments in secondary lymphoid organs and tissue pathophysiologies such as tumor masses?, and (2) how do the characteristics or nutrient sensors in cells alter their function?
Research Description
Research overview:
My lab investigates the molecular mechanisms by which external signals influence lymphocyte function in homeostasis, immunity, and pathophysiology. The sensing of an environment and transduction of its signals regulates transcriptional programs that control the survival, differentiation and proliferation of the cells that endow the immune system with its specificity for foreign antigens. An overall goal is for the investigation of molecular pathways to lead to advances in our understanding and treatment of the myriad diseases in which humoral and cell-mediated immune mechanisms regulate inflammation and pathogenesis.
Our proximate goals are to identify genes involved in the control of lymphocyte function, to target proteins with altered activities to defined populations of lymphocytes in intact mice by using retroviral transduction and transgenic technologies, and to evaluate the effect of these altered activities on immunity, inflammation, and cancer. In recent years, this focus of long standing has sprouted a new branch stimulated by a recognition that while the concentrations and supplies of nutrients and metabolites that surround lymphocytes and other immune system cells can regulate their characteristics and function, this molecular landscape has not been measured. Thus, we have embarked on new means of explorating and quantifying metabolic features of immune micro-environments and plan to test how microbial or cancerous processes influence these features. This new facet of our work will be tied to metabolic sensor networks in immunity, and use existing and new loss-of-function genetic models to test whether and why particular cells in adaptive immunity need such signal transducers to persist or function. Two main areas that we are developing and plan to use as models for a broader principle are (1) humoral immunity and sustained production of auto-antibodies, and (2) tumor immunology – for instance, how do the variegated metabolic micro-environment of tumor masses and nutrient restrictions (e.g., that of oxygen) affect tumor-infiltrating lymphocytes or adjacent tertiary lymphoid structures?
Publications
- Caprara G, Prosperini E, Piccolo V, Sigismondo G, Melacarne A, Cuomo A, Boothby M, Rescigno M, Bonaldi T, Natoli G. PARP14 Controls the Nuclear Accumulation of a Subset of Type I IFN-Inducible Proteins. J. Immunol [print-electronic]. 2018 Apr 4/1/2018; 200(7): 2439-54. PMID: 29500242, PII: jimmunol.1701117, DOI: 10.4049/jimmunol.1701117, ISSN: 1550-6606.
- Raybuck AL, Cho SH, Li J, Rogers MC, Lee K, Williams CL, Shlomchik M, Thomas JW, Chen J, Williams JV, Boothby MR. B Cell-Intrinsic mTORC1 Promotes Germinal Center-Defining Transcription Factor Gene Expression, Somatic Hypermutation, and Memory B Cell Generation in Humoral Immunity. J. Immunol [print-electronic]. 2018 Mar 3/12/2018; PMID: 29531165, PII: jimmunol.1701321, DOI: 10.4049/jimmunol.1701321, ISSN: 1550-6606.
- Kumar A, Gordy LE, Bezbradica JS, Stanic AK, Hill TM, Boothby MR, Van Kaer L, Joyce S. NF-¿B Protects NKT Cells from Tumor Necrosis Factor Receptor 1-induced Death. Sci Rep. 2017 Nov 11/15/2017; 7(1): 15594. PMID: 29142275, PMCID: PMC5688132, PII: 10.1038/s41598-017-15461-y, DOI: 10.1038/s41598-017-15461-y, ISSN: 2045-2322.
- Boothby M, Rickert RC. Metabolic Regulation of the Immune Humoral Response. Immunity. 2017 May 5/16/2017; 46(5): 743-55. PMID: 28514675, PII: S1074-7613(17)30174-7, DOI: 10.1016/j.immuni.2017.04.009, ISSN: 1097-4180.
- Sai J, Owens P, Novitiskiy SV, Hawkins OE, Vilgelm AE, Yang J, Sobolik-Delmaire T, Lavender N, Johnson AC, McClain C, Ayers GD, Kelley MC, Sanders M, Mayer IA, Moses HL, Boothby M, Richmond A. PI3K Inhibition Reduces Mammary Tumor Growth and Facilitates Anti-tumor Immunity and Anti-PD1 Responses. Clin. Cancer Res [print-electronic]. 2016 Dec 12/21/2016; PMID: 28003307, PII: 1078-0432.CCR-16-2142, DOI: 10.1158/1078-0432.CCR-16-2142, ISSN: 1078-0432.
- Iwata H, Goettsch C, Sharma A, Ricchiuto P, Goh WW, Halu A, Yamada I, Yoshida H, Hara T, Wei M, Inoue N, Fukuda D, Mojcher A, Mattson PC, Barabási AL, Boothby M, Aikawa E, Singh SA, Aikawa M. PARP9 and PARP14 cross-regulate macrophage activation via STAT1 ADP-ribosylation. Nat Commun. 2016 Oct 10/31/2016; 7: 12849. PMID: 27796300, PMCID: PMC5095532, PII: ncomms12849, DOI: 10.1038/ncomms12849, ISSN: 2041-1723.
- Cho SH, Raybuck AL, Stengel K, Wei M, Beck TC, Volanakis E, Thomas JW, Hiebert S, Haase VH, Boothby MR. Germinal centre hypoxia and regulation of antibody qualities by a hypoxia response system. Nature [print-electronic]. 2016 Sep 9/8/2016; 537(7619): 234-8. PMID: 27501247, PMCID: PMC5161594, PII: nature19334, DOI: 10.1038/nature19334, ISSN: 1476-4687.
- Zhou W, Zhang J, Goleniewska K, Dulek DE, Toki S, Newcomb DC, Cephus JY, Collins RD, Wu P, Boothby MR, Peebles RS. Prostaglandin I2 Suppresses Proinflammatory Chemokine Expression, CD4 T Cell Activation, and STAT6-Independent Allergic Lung Inflammation. J. Immunol [print-electronic]. 2016 Jul 7/25/2016; PMID: 27456482, PII: jimmunol.1501063, DOI: 10.4049/jimmunol.1501063, ISSN: 1550-6606.
- Boothby M. Signaling in T cells - is anything the m(a)TOR with the picture(s)?. F1000Res. 2016; 5: PMID: 26949528, PMCID: PMC4760271, DOI: 10.12688/f1000research.7027.1.
- Boothby MR, Raybuck AL, Cho SH. Complementing T Cells' Functions: Bringing in Metabolism Matters. Immunity. 2015 Jun 6/16/2015; 42(6): 977-9. PMID: 26084014, PII: S1074-7613(15)00230-7, DOI: 10.1016/j.immuni.2015.06.008, ISSN: 1097-4180.