//Smita S. Iyer
Smita S. Iyer 2018-06-20T10:47:08+00:00

Smita S. Iyer, PhD

Assistant Professor

SVM: Department of Pathology, Microbiology, and Immunology
California National Primate Research Center
Center for Comparative Medicine
University of California, Davis
Davis, CA 95616
(530) 752-4376 Office
(530) 752-2688 Lab
(530) 752-7914 Fax
smiyer@ucdavis.edu

Research Interest: Our lab’s primary research interests center around delineating immunological and molecular mechanisms of CD4 T cell help. Our ultimate goal is to use this information to design an effective HIV vaccine and in parallel understand mechanisms of HIV susceptibility and pathogenesis.

Harnessing TFH cells for HIV vaccine design

Our first goal is to figure out the fundamental cues necessary for inducing effective CD4 T follicular helper cell (TFH) responses in order to generate long-lived anti-HIV antibody. TFH cells are a subset of CD4 T cells that aid B cells in navigating and enduring the unforgiving environment of the germinal center (GC). With help from TFH cells, GC B cells can differentiate to plasma cells which are the source of long-lived antibody – central to the success of the majority of licensed vaccines. Clearly, generating a strong TFH and GC response is a pre-requisite of an effective HIV vaccine. But there is another layer of complexity to grapple with. As it turns out, akin to CD4 T cells, TFH cells skew towards different helper profiles. What we don’t clearly understand is which TFH profile favors the induction of persistent and broadly neutralizing anti-HIV antibodies. One of the projects in the lab tackles this question applying cutting edge immunological approaches using the non-human primate model.

Outsmarting HIV target cells

Our second research goal is to figure out immune attributes of HIV susceptibility with a primary focus on CD4 target cells in the genital and rectal mucosa. The genital and rectal mucosal surfaces constitute the major portal of HIV transmission and yet we know very little about target cells in this compartment. In collaboration with clinicians, our goal is to understand how vaccination modulates the immune environment of the mucosa and whether certain attributes render CD4 T cells more vulnerable to HIV entry. By identifying these highly susceptible CD4 T cells, we can design more effective strategies to prevent HIV infection.

Iyer SS, Sabula MJ, Mehta CC, Haddad LB, Brown NL, Amara RR, Ofotokun I, Sheth AN. Characteristics of HIV target CD4 T cells collected using different sampling methods from the genital tract of HIV seronegative women. PLoS ONE. 2017 Jun 1;12(6):e0178193

Mylvaganam GH, Rios D, Abdelaal HM, Iyer S, Tharp G, Mavinger M, Hicks S, Chahroudi A, Ahmed R, Bosinger SE, Williams IR, Skinner PJ, Velu V, Amara RR. Dynamics of SIV-specific CXCR5+ CD8 T cells during chronic SIV infection. Proc Natl Acad Sci U S A. 2017 Feb 21;114(8):1976-1981

Iyer SS, Gangadhara S, Victor B, Shen Xiaoying, Chen Xuemin, Kasturi S, Sabula M, Labranche C, Reddy P, Tomaras G, Montefiori D, Moss B, Spearman P, Pulendran B, Kozlowski P and Amara R. Virus-like particles displaying trimeric SIV envelope gp160 enhance the breadth of DNA/MVA SIV vaccine induced antibody responses in rhesus macaques. J Virol.12; 90(19): 8842-54.

Velu V, Mylvaganam GH, Gangadhara S, Hong JJ, Iyer SS, Gumber S, Ibegbu C, Villinger G, Amara R. Induction of TH1-biased T Follicular helper cells in lymphoid tissue during chronic simian immunodeficiency virus infection defines functionally distinct germinal center TFH cells J Immunol. 1;197(5):1832-42

Rahman K, Iyer SS. Costimulatory molecules as vaccine adjuvants: to 4-1BB or not to 4-1BB? Cell Mol Immunol. 2014, 1-2.

Rahman K, Desai C, Iyer SS, Thorn NE, Kumar P, Liu Y, Smith T, Neish AS, Li H, Tan S, Wu P, Liu X, Farris AB, Nusrat A, Parkos C, Anania F. Loss of Junctional Adhesion Molecule A Promotes Severe Steatohepatitis in Mice on a Diet High in Saturated Fat, Fructose, and Cholesterol. Gastroenterology. 151(4):733-746

Iyer SS, Gangadhara S, Victor B, Gomez R, Basu R, Hong JJ, Labranche C, Montefiori DC, Villinger F, Moss B, Amara RR. Codelivery of Envelope Protein in Alum with MVA Vaccine Induces CXCR3-Biased CXCR5+ and CXCR5- CD4 T Cell Responses in Rhesus Macaques. J Immunol. 2015;195(3):994-1005.

Iyer SS, Amara RR. DNA/MVA Vaccines for HIV/AIDS. Vaccines 2014, 2, 160-178

Kwa S, Sadagopal S, Shen X, Hong JJ, Gangadhara S, Basu R, Victor B, Iyer SS, LaBranche CC, Montefiori DC, Tomaras GD, Villinger F, Moss B, Kozlowski PA, Amara RR. CD40L-Adjuvanted DNA/MVA SIV Vaccine Enhances Protection Against Neutralization Resistant Mucosal SIV Infection. J Virol. 2015;89(8):4690-5

Penaloza-MacMaster P, Kamphorst A, Wieland A, Araki K, Iyer SS, West EE, Mara L, Yang S, Konieczny BT, Sharpe AH, Freeman GJ, Rudensky AY, Ahmed R. Interplay between regulatory T cells and PD-1 in modulating T cell exhaustion and viral control during chronic LCMV infection.  J Exp Med, 2014 211(9):1905-18.

Iyer SS, Latner DR, Zilliox MJ, McCausland M, Akondy RS, Macmaster-Penaloza P, Hale JS, Ye L, Mohammed AU, Yamaguchi T, Sakaguchi S, Amara RR, Ahmed R. Identification of novel markers for mouse CD4+ T follicular helper cells. EJI, 2013 43(12):3219-32.

Hale JS, Youngblood B, Latner DR, Mohammed AU, Ye L, Akondy RS, Wu T, Iyer SS, Ahmed R. Distinct Memory CD4(+) T Cells with Commitment to T Follicular Helper- and T Helper 1-Cell Lineages Are Generated after Acute Viral Infection.Immunity. 2013 18;38(4):805-17.

Rojas M, Parker RE, Thorn N, Corredor C, Iyer SS, Bueno M, Mroz L, Cardenes N, Mora AL, Stecenko AA, Brigham KL. Stem Cell Res Ther. 2013 Mar 4;4(2):26. Infusion of freshly isolated autologous bone marrow derived mononuclear cells prevents endotoxin-induced lung injury in an ex-vivo perfused swine model.

Iyer SS, Chatraw J, Tan W.G, Wherry EJ, Becker T, Ahmed R, Kapasi Z.  Protein energy malnutrition impairs homeostatic proliferation of memory CD8 T cells. J Immunol. 2012; 1;188(1):77-84.

Penaloza-MacMaster P, Ur Rasheed A, Iyer SS, Yagita H, Blazar BR, Ahmed R.  Opposing effects of CD70 costimulation during acute and chronic lymphocytic choriomeningitis virus infection of mice. J Virol. 2011;85(13):6168-74.

Iyer SS, Jones DP, Brigham KL, Rojas M. Effect of Bone Marrow-Derived Mesenchymal Stem Cells on Endotoxin-Induced Oxidation of Plasma Cysteine and Glutathione in Mice. Stem cells Int. 2010; Article ID 868076.

Shyntum Y, Iyer SS, Tian J, Hao L, Mannery YO, Jones DP, Ziegler TR. Dietary sulfur amino acid supplementation reduces small bowel thiol/disulfide redox state and stimulates ileal mucosal growth after massive small bowel resection in rats. J Nutr. 2009;139(12):2272-8.

Iyer SS, Accardi CJ, Ziegler TR, Blanco RA, Ritzenthaler JD, Rojas M, Roman J, Jones DP. Cysteine redox potential determines pro-inflammatory IL-1beta levels. PLoS ONE. 2009;4(3):e5017.

Iyer SS, Co C, Rojas M. Mesenchymal stem cells and inflammatory lung diseases. Panminerva Med. 2009;51(1):5-16.

Iyer SS, Rojas M. Anti-inflammatory effects of mesenchymal stem cells: novel concept for future therapies. Expert Opin Biol Ther. 2008;8(5):569-81.

Rojas M, Iyer S, Co C, Brigham K Animal models of Lung Injury: Role for Mesenchymal Stem Cells. Stem cells in the respiratory system. Stem Cell Biology and Regenerative Medicine, 2010, 141-158.

Iyer SS, Ramirez AM, Ritzenthaler JD, Torres-Gonzalez E, Roser-Page S, Mora AL, Brigham KL, Jones DP, Roman J, Rojas M. Oxidation of extracellular cysteine/cystine redox state in bleomycin-induced lung fibrosis. Am J Physiol Lung Cell Mol Physiol. 2009;296(1):L37-45.

Iyer SS, Jones DP, Brigham KL, Rojas M. Oxidation of plasma cysteine/cystine redox state in endotoxin induced lung injury. Am J Respir Cell Mol Biol. 2009 Jan;40(1):90-8.

Lin S, Wang D, Iyer S, Ghaleb AM, Shim H, Yang VW, Chun J, Yun CC. The Absence of LPA(2) Attenuates Tumor Formation in an Experimental Model of Colitis-Associated Cancer. Gastroenterology. 2009;136(5):1711-20.

Xu J, Gonzalez ET, Iyer SS, Mac V, Mora AL, Sutliff RL, Reed A, Brigham KL, Kelly P, Rojas M. Use of Senescence-Accelerated Mouse Model in Bleomycin-Induced Lung Injury Suggests That Bone Marrow-Derived Cells Can Alter the Outcome of Lung Injury in Aged Mice. J Gerontol A Biol Sci Med Sci, 2009;64(7):731-9.

Anderson CL, Iyer SS, Ziegler TR, Jones DP. Control of extracellular cysteine/cystine redox state by HT-29 cells is independent of cellular glutathione. Am J Physiol Regul Integr Comp Physiol. 2007 Sep; 293(3): R1069-75.

Xu J, Woods CR, Mora AL, Joodi R, Brigham KL, Iyer S, Rojas M. Prevention of endotoxin-induced systemic response by bone marrow-derived mesenchymal stem cells in mice.Am J Physiol Lung Cell Mol Physiol. 2007;293(1):L131-41.

Akuamoah-Boating LA, Iyer SS, Sales RL, Lokko P, Lartey A, Bressan J, Mattes RD. Effect of peanut oil consumption on energy balance. Journal of Applied Research, 2007; 7(2):185-195.

Coelho SB, Sales RL, Iyer SS, Bressan J, Costa NM, Lokko P, Mattes RD. Effects of peanut oil load on energy expenditure, body composition, lipid profile, and appetite in lean and overweight adults. Nutrition. 2006; 22(6):585-92.

Iyer SS, Boateng LA, Sales RL, Coelho SB, Lokko P, Monteiro JB, Costa NM, Mattes RD. Effects of peanut oil consumption on appetite and food choice. Int J Obes. 2006; 30(4):704-10.

Guerri-Fernandez, Robert

Visiting Scholar

Naharika, Rane

Undergraduate Student

Schmidt, Brian

SRA I

Verma, Anil

Post-Doc