RESEARCH FOCUS
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Lyme disease, Leptospirosis and Vector Biology
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Genetic and antigenic determinants of Borrelia burgdorferi infection
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Pathogenesis of Lyme disease
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Vaccine and diagnostic potentials of select antigens
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Host-pathogen interactions - pathogen receptors in the vector and hosts
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Virulence factors of Leptospira interrogans
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Biology and genetics of Ixodes scapulars ticks
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Anti-Tick Vaccines
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Next-generation therapeutics for Lyme disease
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Use of CRISPR/Cas9 mediated Genome Editing to understand Host-Pathogen Interactions and Immunity
Research Interest
Vector-borne diseases are the highest known cause of global human fatality. Many microbes survive in discrete sets of vertebrate and arthropod hosts and lead to well-known diseases including malaria, yellow fever, encephalitis, sleeping sickness, and leishmaniasis. Our primary research interest is to study microbial pathogenesis and host-pathogen interactions to understand the mechanisms by which arthropod-borne pathogens persist in nature. Ongoing focus of my laboratory is a bacterial pathogen, Borrelia burgdorferi, which is responsible for Lyme disease or Lyme borreliosis , the most prevalent arthropod-borne disease in the United States, and in Europe and parts of Asia. The microbe persists in nature through a tick-rodent infection cycle. B. burgdorferi is transmitted to its natural host (rodents) or to accidental hosts (humans and domestic animals) via ticks belonging to the Ixodes scapularis complex. B. burgdorferi invades and persists in multiple organs in mammals inducing an array of clinical complications. The recent introduction of investigative biology tools in genomics and proteomics have significantly contributed to our ability to unravel the molecular mechanisms of B. burgdorferi persistence in its complex enzootic cycle. In our ongoing research efforts, we have made use of these recent advances to elucidate the molecular details by which B. burgdorferi enters, persists and is transmitted through tick and mammals. Understanding the molecular mechanisms of pathogenesis and special biology at the host pathogen interfaces will contribute towards development of therapeutic strategies to interrupt transmission of vector-borne diseases, for which vaccines are mostly unavailable.
Education
M. Sc (1988) University of Calcutta Ph.D. (1994) University of Calcutta Postdoctoral Training (2002) Yale University
Positions and Employment
1988-1990: Junior Research Fellow, University of Calcutta; 1991-1993: Senior Research Fellow, Labonya Prova Bose trust; 1994-1997: Postdoctoral Fellow, IICB; 1998-2002: Postdoctoral Fellow, Yale University School of Medicine; 2002-2006: Associate Research Scientist, Yale University School of Medicine; 2006-2011: Assistant Professor, University of Maryland, College Park; 2011-Current: Associate Professor, University of Maryland, College Park, 2016-Current: Full Professor, University of Maryland, College Park; 2016-2019, Director, Veterinary Medical Sciences (VMSC) Graduate Program, Project Director, Tick Immunity <https://www.tickimmunity.info> 2018-Current.
Funding
Our past and current research are supported by grants and contracts from NIH-NIAID and NIH-NIAMS, American Heart Association, Arthritis Foundation, DoD, Cohen Foundation, Global Lyme Alliance, MAES and Merck.
Current Lab Members (Updated Spring 2023)
Xiuli Yang, PhD, Research Assistant Professor < xyang1@umd.edu>
Chrysoula Kitsou, PhD, Research Assistant Professor <ckitsou@umd.edu>
Min Zhang, PhD, Faculty Specialist <mzhang23@umd.edu>
Vipin Singh Rana, PhD, Assistant Research Scientist <vrana@umd.edu>
Oleksandra Kepple, Postdoctoral Fellow <okepple@umd.edu>
Kathryn Nassar, B.S., Research Coordinator <knassar@umd.edu>
Shraboni Dutta M.Sc, Graduate (PhD) Student <shraboni@umd.edu>
Sandhya Bista, BVSc. Graduate (PhD) Student <sbista1@umd.edu>
Michael Ronzetti, B.S., GPP Graduate (PhD) Student, NIH/UMD <ronzetti@terpmail.umd.edu>
Kazi Antara M.Sc, Graduate (PhD) Student <krantara@umd.edu>
Bibek Bhattachan, BVSc. Graduate (PhD) Student <bbek2020@umd.edu>
Kruthi Vavilikolanu, B.Sc, Graduate (PhD) Student <kvavilik@umd.edu>
Molly Thompson, B.S., Graduate (PhD) Student <mthomp98@umd.edu>
Rachel Lipman, B.S., Graduate (PhD) Student <rmlipman@umd.edu>
Recent Selected Lab publications
Rana VS, Kitsou C, Dutta S, Ronzetti MH, Zhang M, Bernard Q, Smith AA, Tomás-Cortázar J, Yang X, Wu MJ, Kepple O, Li W, Dwyer JE, Matias J, Baljinnyam B, Oliver JD, Rajeevan N, Pedra JHF, Narasimhan S, Wang Y, Munderloh U, Fikrig E, Simeonov A, Anguita J, Pal U. Dome1-JAK-STAT signaling between parasite and host integrates vector immunity and development. Science. 2023 Jan 13;379(6628):eabl3837. doi: 10.1126/science.abl3837. PMID: 36634189.
De S, Kingan SB, Kitsou C, Portik DM, Foor SD, Frederick JC, Rana VS, Paulat NS, Ray DA, Wang Y, Glenn TC, Pal U. A high-quality Ixodes scapularis genome advances tick science. Nature Genetics. 2023 Jan 19. doi: 10.1038/s41588-022-01275-w
O'Neal AJ, Singh N, Rolandelli A, Laukaitis H, Wang X, Shaw DK, Young BD, Narasimhan S, Dutta S, Snyder GA, Samaddar S, Marnin L, Butler LR, Mendes MT, Paz FEC, Valencia LM, Sundberg EJ, Fikrig E, Pal U, Weber DJ, Pedra JHF. Croquemort Elicits Activation of the Immune Deficiency Pathway in Ticks. PNAS, in press. 2023. .
Ronzetti MH, Baljinnyam B, Jalal I, Pal U, Simeonov A. Application of biophysical methods for improved protein production and characterization: a case study on an HtrAfamily bacterial protease. Protein Sci. 2022 Dec;31(12):e4498.
Thakur M, Bista S, Foor SD, Dutta S, Yang X, Ronzetti M, Rana VS, Kitsou C, Linden SB, Altieri AS, Baljinnyam B, Nelson DC, Simeonov A, Pal U. Controlled Proteolysis of an Essential Virulence Determinant Dictates Infectivity of Lyme Disease Pathogens. Infect Immun. 2022 May 19;90(5):e0005922.
Kitsou C, Fikrig E, Pal U. Tick host immunity: vector immunomodulation and acquired tick resistance. Trends Immunol. 2021 Jul;42(7):554-574. doi: 10.1016/j.it.2021.05.005. Epub 2021 May 30. PMID: 34074602. [Feature Review & selected as cover image: https://www.cell.com/trends/immunology/issue?pii=S1471-4906(20)X0008-1]
Rana VS, Kitsou C, Dumler JS, Pal U. Immune evasion strategies of major tick-transmitted bacterial pathogens. Trends Microbiol. 2023 Jan;31(1):62-75. doi: 10.1016/j.tim.2022.08.002. Epub 2022 Aug 31.
Koči J, Bista S, Chirania P, Yang X, Kitsou C, Rana VS, Yas OB, Sonenshine DE, Pal U. Antibodies against EGF-like domains in Ixodes scapularis BM86 orthologs impact tick feeding and survival of Borrelia burgdorferi. Sci Rep. 2021 Mar 17;11(1):6095. doi: 10.1038/s41598-021-85624-5. PMID: 33731754.
Klouwens MJ, Trentelman JJ, Ersoz JI, Nieves Marques Porto F, Sima R, Hajdusek O, Thakur M, Pal U, Hovius JW. Investigating BB0405 as a novel Borrelia afzelii vaccination candidate in Lyme borreliosis. Sci Rep. 2021 Feb 26;11(1):4775. doi: 10.1038/s41598-021-84130-y. PMID: 33637813.
Yang X, Koči J, Smith AA, Zhuang X, Sharma K, Dutta S, Rana VS, Kitsou C, Yas OB, Mongodin EF, Pal U. A novel tick protein supports integrity of gut peritrophic matrix impacting existence of gut microbiome and Lyme disease pathogens. Cell Microbiol. 2021 Feb;23(2):e13275. doi: 10.1111/cmi.13275. Epub 2020 Oct 21. PMID: 33006213.
[Selected as cover and Editor's Choice Article: https://onlinelibrary.wiley.com/doi/10.1111/cmi.13308]
De S, Kitsou C, Sonenshine DE, Pedra JHF, Fikrig E, Kassis JA, Pal U. Epigenetic Regulation of Tick Biology and Vectorial Capacity. Trends Genet. 2021 Jan;37(1):8-11. doi: 10.1016/j.tig.2020.09.012. Epub 2020 Oct 2. PMID: 33020021.
Bista S, Singh P, Bernard Q, Yang X, Hart T, Lin Y, Kitsou C, Rana VS, Zhang F, Linhardt RJ, Zhnag K, Akins DR, Hritzo L, Kim Y, Grab DJ, Dumler JS and Pal U. A novel laminin-binding protein mediates microbial-endothelial cell interactions and facilitates dissemination of Lyme disease pathogens. J Infect Dis 221(9):1438-1447, 2020.
Bernard Q, Thakur M, Smith AA, Kitsou C, Yang X and Pal U. Borrelia burgdorferiprotein interactions critical for microbial persistence in mammals. Cell Microbiol 21(2):e12885,2019
Bernard Q, Smith AA, Yang X, Koci J, Foor SD, Cramer SD, Zhuang X, Dwyer JE, Lin Y, Mongodin E, Marques A, Leong JM, Anguita J and Pal U. Plasticity in early immune evasion strategies of a bacterial pathogen. Proc Natl Acad Sci USA [Epub ahead of print] doi: 10.1073/pnas.1718595115. 2018.
Tang X, Cao Y, Arora G, Hwang J, Sajid A, Brown CL, Mehta S, Marín-López A, Chuang YM, Wu MJ, Ma H, Pal U, Narasimhan S, Fikrig E. The Lyme disease agent co-opts adiponectin receptor-mediated signaling in its arthropod vector. Elife. 2021 Nov 16;10:e72568. PMID: 34783654.
Kitsou C, Foor SD, Dutta S, Bista S, Pal U. Tick gut barriers impacting tick-microbe interactions and pathogen persistence. Mol Microbiol. 2021 Nov;116(5):1241-1248. Epub 2021 Oct 6. PMID: 34570926.
Sajid A, Matias J, Arora G, Kurokawa C, DePonte K, Tang X, Lynn G, Wu MJ, Pal U, Strank NO, Pardi N, Narasimhan S, Weissman D, Fikrig E. mRNA vaccination induces tick resistance and prevents transmission of the Lyme disease agent. Sci Transl Med. 2021 Nov 17;13(620):eabj9827. Epub 2021 Nov 17. PMID: 34788080.
Koci J, Bernard Q, Yang X, and Pal U. Borrelia burgdorferi surface protein Lmp1 facilitates pathogen dissemination through ticks as studied by an artificial membrane feeding system. Sci Rep 8: 1910, 2018.
Singh P, Verma D, Backstedt BT, Kaur S, Kumar M, Smith AA, Sharma K, Yang K, Azevedo JF, Gomes-Solecki M, Buyuktanir O, and Pal U. Borrelia burgdorferi BBI39 paralogs are targets of protective immunity inducing microbicidal responses and reducing pathogen persistence either in hosts or in the vector. J Infect Dis 215: 1000-1009, 2017
Thakur M, Sharma K, Chao K, Smith AA, Herzberg O and Pal U. A protein-protein interaction dictates Borrelial infectivity. Sci Rep 7: 2932. 2017.
Smith AA, Navasa N, Yang X, Wilder CN, Buyuktanir O, Marques A, Anguita J, Pal U. Cross-Species Interferon Signaling Boosts Microbicidal Activity within the Tick Vector. Cell Host Microbe 20: 91-8, 2016
Yang X, Lin Y, Heselpoth RD, Buyuktanir O, Qin J, Kung F, Nelson DN, Leong JM, and Pal U. Middle region of a Borrelia burgdorferi surface protein interacts with host chondroitin-6-sulfate and independently facilitates infection. Cell Microbiol 18: 97-110., 2016.
Kung F Kaur S, Smith AA, Yang X, Wilder CN, Sharma K, Buyuktanir O, and Pal U. A Borrelia burgdorferi surface-exposed transmembrane protein lacking detectable immune responses supports pathogen persistence and constitutes a vaccine target. J Infect Dis 213: 1786-95, 2016.
Ye M, Sharma K, Thakur M, Smith AA, Buyuktanir O, Xiang X, Yang X, Promnares K, Lou Y, Yang XF, Pal U. HtrA, a Temperature- and Stationary Phase-Activated Protease Involved in Maturation of a Key Microbial Virulence Determinant, Facilitates Borrelia burgdorferi Infection in Mammalian Hosts. Infect Immun 84: 2372-81, 2016
Kariu T, Sharma K, Singh P, Smith AA, Backstedt BT, Buyuktanir O, and Pal U. BB0323 and novel virulence determinant BB0238: Borrelia burgdorferi proteins that interact with and stabilize each other and are critical for infectivity. J Infect Dis 211: 462-71, 2015.
Smith AA and Pal U. Immunity-related genes in Ixodes scapularis – perspectives from genome information. Front Cell Infect Microbiol 4: 116, 2014. Review article.
Yang X, Smith AA, Williams MS, and Pal U. A Dityrosine Network Mediated by Dual Oxidase and Peroxidase Influences the Persistence of Lyme Disease Pathogens within the Vector. J Biol Chem 289: 12813-22, 2014. < Published with Journal Cover image >
Complete List of Published Work in MyBibliography
