Avinash Bhandoola

faculty photo
Professor of Pathology and Laboratory Medicine
Department: Pathology and Laboratory Medicine
Graduate Group Affiliations

Contact information
277 John Morgan Building
3620 Hamilton Walk
Philadelphia, PA 19104
Office: (215) 573-0274
Fax: (215) 573-2350
Education:
M.B., B.S. (Medicine)
Grant Medical College, Bombay, India, 1986.
Ph.D. (Immunology)
University of Pennsylvania (1988-1994), 1994.
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Description of Research Expertise

Research Interests:

T cell development; The establishment and maintenance of T cell identity; T cell regeneration.

T cells play essential roles in immune responses. We study how these functional abilities of T cells are acquired during their development. Like other blood cells, T cells originate from blood stem cells resident in the bone marrow. Uniquely among blood cells, their development completes at a distinct anatomical site, the thymus. We're interested in the mechanisms by which some hematopoietic progenitor cells migrate to the thymus. We're further interested in the the transcriptional mechanisms in the thymus that direct the earliest thymus colonizing progenitors down the T cell lineage. We hope to understand the regulatory and developmental logic that establishes a functioning immune system.

Current projects in the laboratory include:
(1) Migration of hematopoietic progenitors to the thymus.
Signals that permit circulating hematopoietic progenitors to selectively settle within the thymus from the blood, and how these signals change during thymic regeneration We're interested in whether chronic inflammation degrades T cell development, why this occurs, and whether ectopic expression of homing molecules can be used to enhance migration to the thymus.
(Schwarz and Bhandoola, Nature Immunology, 2004; Zlotoff et al., Blood, 2010; Zlotoff, Zhang, et al., Blood, 2011; Sultana et al., J Immunol., 2012)

(2) Transcription factors that establish and maintain T-cell specific gene expression.
TCF-1 and HES-1 are transcription factors that impose T cell identity early in T cell development, but the mechanisms employed are uncertain, and are the focus of intense investigation in our laboratory. We currently think HES-1 represses genes involved in development of non-T cell lineages, whereas TCF-1 may drive T-lineage specific gene expression. We're using conditional alleles of TCF-1 to determine whether TCF-1 controls expression of a common set of T cell genes throughout development, or if TCF-1 instead plays different roles in mature T cells.
(Sambandam et al., Nature Immunology, 2005; Weber, Chi, et al., Nature, 2011; De Obaldia et al., Blood, 2013; De Obaldia et al., Nature Immunology, 2013)

(3) The development and function of Innate lymphoid cells.
Innate lymphoid cells have transcriptional programs that appear to mirror those of T cells. The comparison of innate lymphocyte cell development with T cell development provides an opportunity to understand the factors that underlie the shared as well as the unique features and functions of these apparently closely related cell lineages.
(Yang et al., J Immunol, 2011; Yang et al., Immunity, 2013)

Lab Personnel:
Maria Elena De Obaldia
Shirley Zhang
Qi Yang
Christelle Harly
Jerrod Bryson
Xinxin Wang
Mufei Liu
Avinash Bhandoola

Selected Publications

De Obaldia ME, Bell JJ, Bhandoola A: Early T-cell progenitors are the major granulocyte precursors in the adult mouse thymus. Blood 121(1): 64-71, January 2013.

Yang Q, Monticelli LA, Saenz SA, Chi AWS, Sonnenberg GF, Tang J, De Obaldia ME, Bailis W, Bryson JL, Toscano K, Huang J, Haczku A, Pear WS, Artis D, Bhandoola A: T Cell Factor 1 Is Required for Group 2 Innate Lymphoid Cell Generation. Immunity 38(4): 694-704, April 2013.

Yang Q, Saenz S, Zlotoff DA, Artis D, Bhandoola A: Cutting Edge: Natural helper cells derive from lymphoid progenitors. J Immunol. 187(11): 5505-9, October 2011.

Weber BN, Chi AW, Chavez A, Yashiro-Ohtani Y, Yang Q, Shestova O, Bhandoola A: A critical role for TCF-1 in T-lineage specification and differentiation. Nature 476(7358): 63-8, August 2011.

Zlotoff DA, Zhang SL, De Obaldia ME, Hess PE, Todd SP, Logan TD, Bhandoola A : Delivery of progenitors to the thymus limits T-lineage reconstitution after bone marrow transplantation. Blood 118(7): 1962-70, June 2011.

Zlotoff DA, Sambandam A, Logan TD, Bell JJ, Schwarz BA, Bhandoola A: CCR7 and CCR9 together recruit hematopoietic progenitors to the adult thymus. Blood 115(10): 1897-905, March 2010.

Bell JJ , Bhandoola A: The earliest thymic progenitors for T cells possess myeloid lineage potential. Nature 452(7188): 764-7, Apr 2008.

Sambandam A, Maillard I, Zediak VP, Xu L, Gerstein RM, Aster JC, Pear WS, Bhandoola A: Notch signaling controls the generation and differentiation of early T lineage progenitors. Nat Immunol. 6(8): 663-70, August 2005.

Bhandoola A, Artis D: Rebuilding the thymus. Science 336(6077): 40-1, Apr 2012.

Zhang SL, Bhandoola A: Losing TREC with Age. Immunity 36(2): 163-5, Feb 2012.

Love PE, Bhandoola A: Signal integration and crosstalk during thymocyte migration and emigration. Nat Rev Immunol. 11(7): 469-77, June 2011.

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Last updated: 03/10/2014
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