Lee Ann Garrett-Sinha PhD
Lee Ann Garrett-Sinha
PhD
Professor
Jacobs School of Medicine & Biomedical Sciences
Specialty/Research Focus
Autoimmunity; Cell growth, differentiation and development; Gene Expression; Immunology; Molecular and Cellular Biology; Molecular genetics; Signal Transduction; Transcription and Translation; Transgenic organisms
Professional Summary:
As a faculty member at the University of Buffalo, I have studied the signaling pathways and transcriptional networks that regulate the differentiation of immune cells such as B and T lymphocytes and how they are impaired in autoimmune diseases. These studies have been funded both by the NIH and by private foundations including the Lupus Research Institute, the Alliance for Lupus Research, the International Myeloma Foundation and the American Cancer Society. I have been particularly interested in identifying the roles of the transcription factor Ets1 in B cell differentiation and B cell tolerance to self-antigens. Mice lacking Ets1 develop an autoimmune disease with similarities to human lupus and the human Ets1 gene has been identified as a susceptibility locus for a number of different human autoimmune diseases. To mechanistically understand how Ets1 regulates immune cell function and prevents development of autoimmune disease, my lab has extensively investigated the phenotypes of mice lacking Ets1 either globally or in B cells to identify pathways and target genes that are important in the autoimmune phenotype. My lab has also been interested in signaling pathways that regulate the expression and activity of immune cells, including the BCR signaling pathway, Toll-like receptor pathways, the CD22/SHP1 inhibitory pathway and the Notch pathway. Recently, we've developed an interest in the B cell co-receptor signaling pathway involving CD19/CD21 binding to C3d deposited on the surface of pathogens. We also have an interest in understanding how Ets1 cooperates with IL17RA signaling to regulate skin immune responses to bacterial infection.
Education and Training:
- Fellowship, Immunology, University of Chicago (2001)
- PhD, Molecular Biology, University of Texas (1996)
- BA, Biology/Biochemistry, Rice University (1989)
Employment:
- Professor, Biochemistry, State University of New York at Buffalo Jacobs School of Medicine & Biomedical Sciences (2017-present)
- Associate Professor, Biochemistry, SUNY at Buffalo Jacobs School of Medicine & Biomedical Sciences (2011-present)
- Assistant Professor, Biochemistry, SUNY at Buffalo Jacobs School of Medicine & Biomedical Sciences (2001–2011)
- Postdoctoral Research Associate, Department of Medicine, University of Chicago (1999–2001)
- Post Doctoral Fellow, Department of Medicine, Howard Hughes Medical Institute at the University of Chicago (1996–1999)
- Graduate Student, Molecular Genetics, University of Texas Health Sciences Center at Houston (1990–1996)
Awards and Honors:
- Laboratory Travel Grant (2021)
- Travel Grant to the International Congress of Immunology, Melbourne, Australia (2016)
Research Expertise:
- Autoimmune Disease: Analysis of Autoantibody Levels Analysis of B and T cell Activation Analysis of B cell tolerance to self-antigen
- B cell receptor signaling: Western blotting Immunoprecipitation Ca2+ mobilization
- Skin Immune responses: T cell responses to bacterial infection
- Squamous Cell Carcinoma: Mouse models of Squamous cell cancer Analysis of Skin phenotypes
- Transgenic/Knockout Mice: Generation, breeding and analysis of transgenic and knockout mouse strains
Research Centers:
- Witebsky Center for Microbial Pathogenesis and Immunology
UB 2020 Strategic Strengths:
- Molecular Recognition in Biological Systems and Bioinformatics
Grants and Sponsored Research:
- July 2022–June 2027
Molecular mechanisms of skin immunity to Staphylococcal infection
NIH
Role: Co-Principal Investigator
$527,503 - July 2022–June 2024
A novel model to investigate CD19 cooperation with BCR signaling
NIH
Role: Principal Investigator
$198,803 - December 2021–November 2022
Ets1 and IL17RA Role in Skin Immunity
P30 Project grant awarded to Mt. Sinai for pilot studies on dermatology
Role: Principal Investigator
$40,000 - April 2016–March 2022
Regulation and Consequences of Ets1 Downregulation in B Cells
NIH
Role: Co-Investigator - January 2016–December 2018
Understanding the Pathway Regulated by the Lupus Susceptibility Gene Ets1
Lupus Research Alliance
Role: Co-Investigator - May 2010–April 2015
Identification of Specific Roles for Ets-1 in B Cell Tolerance
NIAID, NIH
Role: Principal Investigator - April 2012–March 2014
Functional Relationships Between the Lupus Susceptibility Loci Lyn and Ets1
National Institutes of Health
Role: Co-Investigator - August 2011–July 2013
Functional Relationships Between the Lupus Susceptibility Loci Lyn and Ets1
Alliance for Lupus Research
Role: Co-Investigator
Journal Articles:
- Sunshine, A.C., Goich, D., Stith, A., Sortino, K., Dalton, J., Metcalfe, S., Svensson, E. and *Garrett-Sinha, L.A. (2019) Ets1 controls the development of B cell autoimmune responses in a cell-autonomous manner. Immunohorizons (Jul), 7(3): 331-340. doi:10.4049/immunohorizons.1900033
- Gluck, C., Tsompana, M., Nowak, N., Garrett-Sinha, L.A., Buck, M. and Sinha, S. (2019) Molecular Dissection of the Oncogenic Role of ETS1 in the Mesenchymal Subtypes of Head and Neck Squamous Cell Carcinoma. PLoS Genet (Jul), 7(15) doi:10.1371/journal.pgen.1008250
- Noviski M, Mueller JL, Satterthwaite A, Garrett-Sinha LA, Brombacher F, Zikherman J, Garrett-Sinha L. (2018) IgM and IgD B cell receptors differentially respond to endogenous antigens and control B cell fate. Elife (Mar), 7.
- Willis SN, Tellier J, Liao Y, Trezise S, Light A, O'Donnell K, Garrett-Sinha LA, Shi W, Tarlinton DM, Nutt SL, Garrett-Sinha L. (2017) Environmental sensing by mature B cells is controlled by the transcription factors PU.1 and SpiB. Nat Commun (Nov), 8(1): 1426-1426.
- Saelee P, Kearly A, Nutt SL, Garrett-Sinha LA, Garrett-Sinha L. (2017) Genome-Wide Identification of Target Genes for the Key B Cell Transcription Factor Ets1. Front Immunol (Apr), 8: 383-383.
- Garrett-Sinha LA, Kearly A, Satterthwaite AB, Garrett-Sinha L. (2016) The Role of the Transcription Factor Ets1 in Lupus and Other Autoimmune Diseases. Crit Rev Immunol (Jan), 36(6): 485-510.
- Russell L, John S, Cullen J, Luo W, Shlomchik MJ, Garrett-Sinha LA, Garrett-Sinha L. (2015) Requirement for Transcription Factor Ets1 in B Cell Tolerance to Self-Antigens. J Immunol (Oct), 195(8): 3574-3583.
- Mayeux J, Skaug B, Luo W, Russell LM, John S, Saelee P, Abbasi H, Li QZ, Garrett-Sinha LA, Satterthwaite AB, Garrett-Sinha L. (2015) Genetic Interaction between Lyn, Ets1, and Btk in the Control of Antibody Levels. J Immunol (Sep), 195(5): 1955-1963.
- Rozanski CH, Utley A, Carlson LM, Farren MR, Murray M, Russell LM, Nair JR, Yang Z, Brady W, Garrett-Sinha LA, Schoenberger SP, Green JM, Boise LH, Lee KP, Garrett-Sinha L. (2015) CD28 Promotes Plasma Cell Survival, Sustained Antibody Responses, and BLIMP-1 Upregulation through Its Distal PYAP Proline Motif. J Immunol (May), 194(10): 4717-4728.
- Yuan X, Garrett-Sinha LA, Sarkar D, Yang S, Garrett-Sinha L. (2014) Deletion of IFT20 in early stage T lymphocyte differentiation inhibits the development of collagen-induced arthritis. Bone Res (Nov), 2: 14038-14038.
- Luo W, Mayeux J, Gutierrez T, Russell L, Getahun A, Müller J, Tedder T, Parnes J, Rickert R, Nitschke L, Cambier J, Satterthwaite AB, Garrett-Sinha LA, Garrett-Sinha L. (2014) A balance between B cell receptor and inhibitory receptor signaling controls plasma cell differentiation by maintaining optimal Ets1 levels. J Immunol (Jul), 193(2): 909-920.
- John S, Russell L, Chin SS, Luo W, Oshima R, Garrett-Sinha LA, Garrett-Sinha L. (2014) Transcription factor Ets1, but not the closely related factor Ets2, inhibits antibody-secreting cell differentiation. Mol Cell Biol (Feb), 34(3): 522-532.
- Agudo J, Ruzo A, Tung N, Salmon H, Leboeuf M, Hashimoto D, Becker C, Garrett-Sinha LA, Baccarini A, Merad M, Brown BD, Garrett-Sinha L. (2014) The miR-126-VEGFR2 axis controls the innate response to pathogen-associated nucleic acids. Nat Immunol (Jan), 15(1): 54-62.
- Chin SS, Romano RA, Nagarajan P, Sinha S, Garrett-Sinha LA, Garrett-Sinha L. (2013) Aberrant epidermal differentiation and disrupted DeltaNp63/Notch regulatory axis in Ets1 transgenic mice. Biol Open (Dec), 2(12): 1336-1345.
- Huntoon KM, Russell L, Tracy E, Barbour KW, Li Q, Shrikant PA, Berger FG, Garrett-Sinha LA, Baumann H, Garrett-Sinha L. (2013) A unique form of haptoglobin produced by murine hematopoietic cells supports B-cell survival, differentiation and immune response. Mol Immunol (Oct), 55(3-4): 345-354.
- Garrett-Sinha LA, Garrett-Sinha L. (2013) Review of Ets1 structure, function, and roles in immunity. Cell Mol Life Sci (Sep), 70(18): 3375-3390.
- DeKoter RP, Geadah M, Khoosal S, Xu LS, Thillainadesan G, Torchia J, Chin SS, Garrett-Sinha LA, Garrett-Sinha L. (2010) Regulation of follicular B cell differentiation by the related E26 transformation-specific transcription factors PU.1, Spi-B, and Spi-C. J Immunol (Dec), 185(12): 7374-7384.
- Nagarajan P, Chin SS, Wang D, Liu S, Sinha S, Garrett-Sinha LA, Garrett-Sinha L. (2010) Ets1 blocks terminal differentiation of keratinocytes and induces expression of matrix metalloproteases and innate immune mediators. J Cell Sci (Oct), 123(Pt 20): 3566-3575.
- Russell L, Garrett-Sinha LA, Garrett-Sinha L. (2010) Transcription factor Ets-1 in cytokine and chemokine gene regulation. Cytokine (Sep), 51(3): 217-226.
- Ye M, Coldren C, Liang X, Mattina T, Goldmuntz E, Benson DW, Ivy D, Perryman MB, Garrett-Sinha LA, Grossfeld P,. (2010) Deletion of ETS-1, a gene in the Jacobsen syndrome critical region, causes ventricular septal defects and abnormal ventricular morphology in mice. Hum Mol Genet (Feb), 19(4): 648-656.
- John SA, Garrett-Sinha LA, Garrett-Sinha L. (2009) Blimp1: a conserved transcriptional repressor critical for differentiation of many tissues. Exp Cell Res (Apr), 315(7): 1077-1084.
- Nagarajan, P., Parikh, N., Garrett-Sinha, L.A., Sinha, S. (2009) Ets1 induces dysplastic changes when expressed in terminally-differentiating squamous epithelial cells. PLoS One (Jan), 4(1): e4179.
- Nagaleekar VK, Diehl SA, Juncadella I, Charland C, Muthusamy N, Eaton S, Haynes L, Garrett-Sinha LA, Anguita J, Rincón M, Garrett-Sinha L. (2008) IP3 receptor-mediated Ca2+ release in naive CD4 T cells dictates their cytokine program. J Immunol (Dec), 181(12): 8315-8322.
- Parikh, N., Nagarajan, P., Sei-Ichi, M., Sinha, S., Garrett-Sinha, L.A. (2008) Isolation and characterization of an immortalized oral keratinocyte cell line of mouse origin. Arch Oral Biol (Nov), 53(11): 1091-1100.
- Garrett-Sinha LA, John, S.A., Gaffen, S. (2008) IL-17 and the Th17 lineage in SLE. Curr Opin Rheumatol (Sep), 20(5): 519-525.
- Landesberg R, Cozin M, Cremers S, Woo V, Kousteni S, Sinha S, Garrett-Sinha L, Raghavan S. (2008) Inhibition of oral mucosal cell wound healing by bisphosphonates. J Oral Maxillofac Surg (May), 66(5): 839-847.
- John, S.A., Clements, J.L., Russell, L.M., Garrett-Sinha, L.A. (2008) Ets-1 regulates plasmacytic differentiation by interfering with the activity of the transcription factor Blimp-1. J Biol Chem (Jan), 283(2): 951-962.
- Clements, J.L., John, S.A., Garrett-Sinha, L.A. (2006) Impaired generation of CD8 thymocytes in Ets-1-deficient mice. J Immunol (Jul), 177(2): 905-912.
- Wang, D., John, S.A., Clements, J.L., Percy, D.H., Barton, K.P., Garrett-Sinha, L.A. (2005) Ets-1 deficiency leads to altered B cell differentiation, hyper-responsiveness to TLR9 and autoimmune disease. Int Immunol (Sep), 17(9): 1179-1191.
- Garrett-Sinha LA, Hou, P., Wang, D., Grabiner, B., Araujo, E., Rao, S., Yun, T.J., Clark, E.A., Simon, M.C., Clark, M.R. (2005) Spi-1 and Spi-B control the expression of the Grap2 gene in B cells. Gene (Jun), 353(1): 134-146.
- Lefebvre, J.M., Haks, M.C., Carleton, M.O., Rhodes, M., Simon, M.C., Eisenlohr, L.C., Garrett-Sinha, L.A., Wiest, D.L. (2005) Enforced expression of Spi-B reverses T lineage commitment and blocks beta-selection. J Immunol (May), 174(10): 6184-6194.
- Hu CJ, Rao S, Ramirez-Bergeron DL, Garrett-Sinha LA, Gerondakis S, Clark MR, Simon MC. (2001) PU.1/Spi-B regulation of c-rel is essential for mature B cell survival. Immunity (Oct), 15(4): 545-555.
- Garrett-Sinha LA, Dahl R, Rao S, Barton KP, Simon MC. (2001) PU.1 exhibits partial functional redundancy with Spi-B, but not with Ets-1 or Elf-1. Blood (May), 97(9): 2908-2912.
- Fischer EA, Verpont MC, Garrett-Sinha LA, Ronco PM, Rossert JA. (2001) Klf6 is a zinc finger protein expressed in a cell-specific manner during kidney development. J Am Soc Nephrol (Apr), 12(4): 726-735.
- Rao S, Garrett-Sinha LA, Yoon J, Simon MC, Sinha LA. (1999) The Ets factors PU.1 and Spi-B regulate the transcription in vivo of P2Y10, a lymphoid restricted heptahelical receptor. J Biol Chem (Nov), 274(48): 34245-34252.
- Garrett-Sinha LA, Su GH, Rao S, Kabak S, Hao Z, Clark MR, Simon MC, Sinha LA. (1999) PU.1 and Spi-B are required for normal B cell receptor-mediated signal transduction. Immunity (Apr), 10(4): 399-408.
- Inagaki Y, Truter S, Bou-Gharios G, Garrett LA, de Crombrugghe B, Nemoto T, Greenwel P, Sinha LA. (1998) Activation of Proalpha2(I) collagen promoter during hepatic fibrogenesis in transgenic mice. Biochem Biophys Res Commun (Sep), 250(3): 606-611.
- Su GH, Chen HM, Muthusamy N, Garrett-Sinha LA, Baunoch D, Tenen DG, Simon MC, Sinha LA. (1997) Defective B cell receptor-mediated responses in mice lacking the Ets protein, Spi-B. EMBO J (Dec), 16(23): 7118-7129.
- Garrett-Sinha LA, Eberspaecher H, Seldin MF, de Crombrugghe B, Sinha LA. (1996) A gene for a novel zinc-finger protein expressed in differentiated epithelial cells and transiently in certain mesenchymal cells. J Biol Chem (Dec), 271(49): 31384-31390.
- Bou-Gharios G, Garrett LA, Rossert J, Niederreither K, Eberspaecher H, Smith C, Black C, Crombrugghe B, Sinha LA. (1996) A potent far-upstream enhancer in the mouse pro alpha 2(I) collagen gene regulates expression of reporter genes in transgenic mice. J Cell Biol (Sep), 134(5): 1333-1344.
- Hasegawa T, Zhou X, Garrett LA, Ruteshouser EC, Maity SN, de Crombrugghe B, Sinha LA. (1996) Evidence for three major transcription activation elements in the proximal mouse proalpha2(I) collagen promoter. Nucleic Acids Res (Aug), 24(16): 3253-3260.
- Rossert JA, Garrett LA, Sinha LA. (1995) Regulation of type I collagen synthesis. Kidney Int Suppl (Jun), 49: 34-38.
- Goldberg H, Helaakoski T, Garrett LA, Karsenty G, Pellegrino A, Lozano G, Maity S, de Crombrugghe B, Sinha LA. (1992) Tissue-specific expression of the mouse alpha 2(I) collagen promoter. Studies in transgenic mice and in tissue culture cells. J Biol Chem (Sep), 267(27): 19622-19630.
- Ali Seifinejad, Almar Neiteler, Sha Li, Corinne Pfister, Rolf Fronczek, Ling Shan, Lee A. Garrett-Sinha, David Frieser, Makoto Honda, Yoan Arribat, Dogan Grepper, Francesca Amati, Marie Picot, Christian Iseli, Nicolas Chartrel, Gert J. Lammers, Roland Liblau, Anne Vassalli, Mehdi Tafti. (1900) Narcolepsy with cataplexy is caused by epigenetic silencing of hypocretin neurons. (Jan)
- Sunshine, A.C., Battaglia, M., Luo, W., Jin, R., Stith, A., Lindemann, M, Sinha, S., Wohlfert, E. and Garrett-Sinha, L.A. (1900) The transcription factor Ets1 cooperates with IL17RA signaling to prevent development of auto-immunity and immunodeficiency. Front Immunol (Jan)
- Kearly, A., Ottens, K., Satterthwaite, A. and Garrett-Sinha, L.A. (1900) Ets1 levels in B cells are regulated at the transcriptional level by IKK, but not by the canonical NF?B pathway. (Jan)
Professional Memberships:
- American Society for Microbiology (2013–2014)
- New York Academy of Sciences (2009–2010)
- Developmental Genomics Research Focus Group (2009–2014)
- Buffalo Collegium of Immunologists (2006–2014)
- American Association of Immunologists; Major American Immunology Society (2002–present)
Presentations:
- "Roles of Ets1 and IL17RA in regulating skin immune responses to Staphylococcus aureus infection" UB Department of Microbiology, Witebsky Center (2021)
- "Ets1 – a Human Lupus-Susceptibility Gene that Regulates B Cell Function" Roswell Park Tumor Immunology and Immunotherapy Retreat (2019)
Service Activities:
- Reviewer, Clinical and Translational Medicine; Reviewer (2021–present)
- NIH, Cellular and Molecular Immunology A Study Section; Reviewer (2021)
- NIH, Special Emphasis Panel for F07 Immunology Fellowships and AREA Grants; Reviewer (2021)
- Journal of Immunology; Reviewer (2021–present)
- Frontiers in Immunology; Reviewer (2021–present)
- Immunological Investigations; Reviewer (2021–present)
- NIH, Immunity and Host Defense Study Section; Reviewer (2020)
- NIH, Special Emphasis Panel for F07 Immunology Fellowships and AREA Grants; Reviewer (2020)
- NIH, Special Emphasis Panel, ZRG1 IMM-T(02)M; Reviewer (2019)
- NIH, Hypersensitivity, Autoimmunity and Immune-Mediated Diseases Study Section; Reviewer (2019)
- NIH, Autoimmunity Centers of Excellence U19 Review Panel; Reviewer (2019)
- NIH, Cellular and Molecular Immunology B Study Section; ad-hoc Reviewer (2019)
- PhD Program in Biomedical Sciences (PPBS) Admissions Committee; Member (2018–present)
- Associate Editor, Frontiers in Immunology; Reviewer (2017–present)
- Associate Editor, Journal of Immunology; Editor (2014–2017)
- Immunological Investigations; Editorial Board (2010–present)
- IACUC Committee For Roswell Park IACUC; Member (2008–2011)
- Careers Roundtable Discussion Leader AAI Annual meeting in 2007; Contributor (2007)
- Organizing Committee Buffalo Immunology Conference; Chair (2005–2014)
- Buffalo Immunology Conference Organizing Committee; Member (2004–2005)
- Faculty Council Alternate Alternate to faculty Council; Committee Member (2004–2006)
- Buffalo Immunology Conference -2004; Co-Chair (2004)
- Buffalo Immunology Conference Organizing Committee; Co-Chair (2003)
- Medical Student Training Program (MSTP) admissions Committee; Member (2003–2004)
- Member Search Committee for Department of Biology Faculty Search To select and interview candidates for faculty search in the Biology Department; Member (2003–2004)