Stanley Adoro, PhD

Assistant Professor
Department of Pathology
Case Western Reserve University
School of Medicine
Member
Hematopoietic and Immune Cancer Biology Program
Case Comprehensive Cancer Center

Stanley Adoro obtained a B.Sc. in Biochemistry and M.Sc. Cellular Parasitology from the University of Ibadan, Nigeria. He came to the United States for graduate school where he received a Ph.D. in Immunology from the University of Pennsylvania under Dr. Alfred Singer in 2009. During his PhD he uncovered that the unique kinetics of the genetic loci encoding CD4/CD8 coreceptor proteins dictated T-cell lineage fate during T-cell development in the thymus. For his postdoctoral training he joined the laboratory of Dr. Laurie Glimcher at Harvard Medical School (Boston) and later at Weill Cornell Medical College (New York) for postdoctoral training where he began his research interests in how the proteostasis machinery controls the homeostasis and tumorigenesis of blood cells. After a brief stay in Boston as a Faculty Member at Dana Farber Cancer Institute affiliated with Harvard Medical School he joined the Department of Pathology at Case Western Reserve University in 2017. His laboratory is interested in how the cellular proteostasis machinery controls immune cell development, regeneration and blood cancers.

Research Information

Research Interests

Humans and other mammals depend on the timely and lifelong generation of all blood cell lineages from hematopoietic stem cells (HSC) in the bone marrow for their health and survival. However, this lifelong replenishment comes with a continuing challenge for blood cells to maintain a dynamic interaction with their environment whereby they sense and balance their numbers, diversify while adequately responding to the hosts’ needs. Defects in blood cell development are often catastrophic and are the basis of several blood disorders including autoimmunity, immunodeficiencies and a wide array of blood cancers.

Research Projects

Our laboratory seeks to understand the mechanisms that regulate blood cell development and homeostasis with the goal of identifying cellular targets that can be harnessed to improve blood cell regeneration and to alleviate blood cancers. We specifically address how the molecular machinery that controls proteostasis –the fine balance of cellular protein quantity, quality and their posttranslational modifications– regulates immune cells with a specific focus on HSCs and T-cells. For these investigations, we combine innovative genetic mouse models harboring fluorescent reporters of development regulators, inducible “loss- and gain-of-function” alleles of proteostasis genes with relevant human blood cancer models to gain understanding of normal and malignant immune cell homeostasis.

A major area of investigation is to elucidate how unfolded protein response enzymes that normally resolve any stress associated with endoplasmic reticulum protein folding, control HSC differentiation and myeloid leukemogenesis. Another area of research is to understand how the recently described protein substrate stabilizer CHMP5 controls T-cell immunity. Through these studies, we expect to uncover new therapeutic avenues to improve blood cell regeneration and mitigate HSC-derived blood cancers. 

Publications

Adoro S, Park KH, Bettigole SE, Lis R, Shin HR, Park JY, Kim JH, Knobeloch K-P, Shim JH and Glimcher LH. Post-translational control of T cell development by the ESCRT protein CHMP5. Nature Immunology, in press

Bettigole S, Lis R, Adoro S, Weller PF, Lee AH and Glimcher LH. The transcription factor XBP1 is selectively required for eosinophil differentiation. Nature Immunology 16:829-837. 2015.

Adoro S, Cubillos-Ruiz JR, Deruaz M, Vrbanac VD, Song M, Park S, Kwon DS, Murooka TT, Dudek TE, Streeck H, Walker BD, Luster AD, Tager AM, Lazarevic V and Glimcher LH. IL-21 induces antiviral microRNA-29 in CD4 T cells to limit HIV-1 infectionNature Communications 6:7562. 2015.

Chen X, Iliopoulos D, Zhang Q, Tang Q, Greenblatt MB, Hatziapostolou M, Lim E, Tam WL, Ni W, Chen Y, Mai J, Shen H, Hu DZ, Adoro S, Hu B, Song M, Landis MD, Ferrari M, Brown M, Chang JC, Liu SX and Glimcher LH. XBP1 promotes human triple negative breast cancer by controlling the hypoxia responseNature 508:103-1072014.

Adoro S, Park JH and Singer A. Coreceptor gene imprinting”: a genetic solution to a developmental dilemma in T cellsCell Cycle 11:833-834. 2012.

Adoro S, McCaughtry T, Erman B, Alag A, Van Laethem F, Park JH, Tai X, Kimura M, Wang L, Grinberg A, Kubo M, Bosselut R, Love P and Singer A. Coreceptor gene imprinting governs thymocyte lineage fateEMBO Journal 31:366-377. 2012.

Park JH, Adoro S, Guinter T, Erman B, Alag AS, Catalfamo M, Kimura MY, Cui Y, Lucas PJ, Gress RE, Kubo M, Hennighausen L, Feigenbaum L and Singer A. Signaling by intrathymic cytokines, not T cell antigen receptors, specifies CD8 lineage choice and promotes the differentiation of cytotoxic lineage T cellsNature Immunology 11:257-264. 2010.

Singer A, Adoro S and Park JH. Lineage fate and intense debate: myths, models and mechanisms of CD4/CD8 lineage choiceNature Reviews Immunology 8:788-801. 2008.

Adoro S, Erman B, Sarafova S, Van Laethem F, Park JH, Feigenbaum L and Singer A. Targeting CD4 coreceptor expression to post-selection thymocytes reveals that CD4/CD8 lineage choice is neither error-prone nor stochasticJournal of Immunology 181:6975-6983. 2008.

Park JH, Adoro S, Lucas PJ, Sarafova SD, Alag SA, Doan LL, Erman B, Liu X, Ellmeier W, Bosselut R, Feigenbaum L and Singer A. Coreceptor tuning’: cytokine signals transcriptionally tailor CD8 coreceptor expression in CD8 T cells to the self-specificity of their TCRNature Immunology 8:1049-1059. 2007.