Yatin M. Vyas, MD, MBBS

Portrait
Vice Chair of Research
Mary Joy and Jerre Stead Professor of Pediatric Hematology/Oncology
Professor of Pediatrics - Hematology Oncology

Contact Information

Primary Office: 1324 BT
200 Hawkins Drive
Iowa City, IA 52242
319-353-7116

Lab: 3080 ML
Iowa City, IA 52242
319-353-4809

Education

MBBS, Gujarat University, Medicine
MBBS, Gujarat University, Surgery
MD, Gujarat University Civil Hospital, Pediatrics

Resident, Gujarat University Civil Hospital, Pediatrics
Chief Resident, Gujarat University Civil Hospital, Pediatrics
Resident, New York University Medical Center, Bellevue Hospital, Pediatrics
Fellow, Memorial Sloan-Kettering Cancer Center, New York Hospital-Cornell Univeristy Pediatric Hematology/Oncology
Fellow, Memorial Sloan-Kettering Cancer Center, Special Clinical Fellow
Fellow, Sloan-Kettering Institute for Cancer Research, Immunology

Licensure and Certifications

Iowa Medical License - Iowa Board of Medicine
Certified and Recertified, Pediatric Hematology-Oncology - American Board of Pediatrics

Education/Training Program Affiliations

Interdisciplinary Graduate Program in Immunology, Medical Scientist Training Program

Center, Program and Institute Affiliations

Holden Comprehensive Cancer Center

Research Summary

My laboratory research program focuses on explicating the molecular underpinnings of immune dysregulation and cancer development in children. The laboratory is consistently funded by the National Institutes of Health (NIH) through both R01 and R21 mechanisms. Two broad components of our research program are: 1. Wiskott-Aldrich Syndrome and immune dysregulation: I have a longstanding interest in understanding the molecular underpinnings of the development of human immune responses in health and disease. We have chosen to use the genetic disease model of Wiskott-Aldrich syndrome (WAS) to determine the partners and pathways of WAS protein (WASp) participation in the regulation of CD4 T helper cell differentiation and the development of T cell adaptive immunity. Human WAS is an X-linked genetic disease manifesting in severe immune deficiency, autoimmunity, thrombocytopenia, and lymphoid cancers in young boys. In order to clarify WASp’s role in immune regulation in health, and immune dysregulation in WAS, our laboratory has taken the complementary approach of investigating the functions of WASp from both vantage points, i.e. cytoplasm and nucleus. Research from my laboratory was essential in revealing for the first time a novel nuclear function for WASp in the transcriptional regulation of Th1-differentiation through its effect on epigenetic modifications at the T-BET gene-promoter locus. Since that time, we have been actively involved in further understanding how WASp associates with and regulates protein pathways and gene networks that control development of protective type-1 immunity. We seek to explicate the molecular mechanism of WASp’s nuclear transport and its role on impacting Th1/Th2/Th17/Treg differentiation. We are particularly interested in understanding the molecular basis for the disease severity in WAS patients that carry single missense mutations that still allow the expression of mutant WASp. We are testing the hypothesis that the primary function of WASp is in coordinating the nuclear events of gene transcription that occur independently of its well-described cytoplasmic effect on the actin cytoskeleton. We believe our studies will have direct implications to the better design of therapeutics in WAS, a life-threatening childhood disease. 2. Investigating the Genome and Epigenome of Pediatric Acute Lymphoblastic Leukemia (ALL): We have recently embarked on the studies of childhood ALL. Despite an improved understanding of the pathogenesis of childhood ALL from a cellular and molecular perspectives, the current knowledge of how the multiple genetic alterations (mutations, translocations, etc.) associated with ALL modify the disease severity and response to conventional chemotherapy is ill understood. It is also clear whether these genetic mutations are a cause (i.e., a driver event) or a consequence (i.e., a passenger event) for the development of ALL. Do these genetic/epigenetic events contribute directly to the primary treatment failures in childhood ALL is also unclear. Our research is aimed at understanding if and how the genomic and epigenomic landscapes of the leukemic blasts pattern the different severity grades of ALL. Whether such novel metric could be identified and ultimately used clinically to predict children who will respond to chemotherapy versus ones who will not.

Publications

Sarkar, K., Sadhukhan, S., Han, S. S. & Vyas, Y. M. (2015). SUMOylation-disrupting WAS mutation converts WASp from a transcriptional activator to a repressor of NF-?B response genes in T cells. Blood, 126(14), 1670-82. PMID: 26261240.

McNew, B., Rokes, C., Kamberos, N., Abusin, G. & Vyas, Y. M. (2015). Two Rare Cases of Hepatocellular Malignant Neoplasm (HMN) - Not Otherwise Specified (NOS), A Newly Recognized Pediatric Cancer. ASPHO Abstracts.

Sarkar, K., Sadhukhan, S., Han, S. S. & Vyas, Y. M. (2015). SUMOylation-disrupting WAS mutation converts WASp fro a transcriptional activator to a repressor of NF-kB response genes in T cells. Blood.

Anderson, P. M., Meyers, P., Kleinerman, E., Venkatakrishnan, K., Hughes, D. P., Herzog, C., Huh, W., Sutphin, R., Vyas, Y. M., Shen, V., Warwick, A., Heager, N., Oliva, C., Wang, B., Liu, Y. & Chou, A. (2014). Mifamurtide in metastatic and recurrent osteosarcoma: A patient access study with pharmacokinetic, pharmacodynamic, and safety assessments. Pediatr Blood Cancer, 61(2), 238-44. PMID: 23997016.

Sadhukhan, S., Sarkar, K., Taylor, M., Candotti, F. & Vyas, Y. M. (2014). Nuclear Role of WASp in Gene Transcription Is Uncoupled from its ARP2/3-Dependenct Cytoplasmic Role in Actin Polymerization. J Immunol, 193(1), 150-60. PMID: 24872192.

Sarkar, K., Sadhukhan, S., Han, S. & Vyas, Y. M. (2014). Distruption of hSWI/SNF-Complexes in T cells by WAS Mutations Distinguishes X-linked Thrombocytopenia from Wiskott-Aldrich Syndrome. Blood, 124(23), 3409-19. PMID: 25253772.

El-Sheikh, A. A., Hashem, H., Holman, C. & Vyas, Y. M. (2014). Congenital dyserythropoietic anemia type I presenting as persistent pulmonary hypertension and pigeon chest deformity. Pediatr Blood Cancer, 61(8), 1460-2. DOI: 10.1002/pbc.24945.

Vyas, Y. M., Taylor, M. D., Sadhukhan, S., Ramgopal, A., Kottangada, P., Sarkar, K., D'Silva, S., Selvakumar, A. & Candotti, F. (2010). Nuclear Role of WASp in the Pathogenesis of Dysregulated TH1-Immunity in Human Wiskott-Aldrich Syndrome. (Vols. 2). (37), pp. 37-44. SCIENCE Transl Med. PMID: 20574068.

Kreindler, J. L., Steele, C., Nguyen, N., Chan, Y. R., Pilewski, J. M., Alcorn, J. F., Vyas, Y. M., Aujla, S. J., Finelli, P., Blanchard, M., Zeigler, S. F., Logar, A., Hartigan, E., Kurs-Lasky, M., Rockette, H., Ray, A. & Kolls, J. K. (2010). Vitamin D3 attenuates Th2 responses to Aspergillus fumigatus mounted by CD4+ T cells from cystic fibrosis patients with allergic bronchopulmonary aspergillosis. (Vols. 120). (9), pp. 3242-54. J Clin Invest. PMID: 20714107.

Hackney, L., Rodenberg, D. & Vyas, Y. M. (2008). Dysregulation of the Notch signaling pathway in alveolar rhabdomyosarcoma. Annual AACR meeting 2008.

Rodenberg, D., Davicioni, E., Hackney, L., Triche, T. & Vyas, Y. M. (2008). Disparate Expression of Notch 1 and Notch 2 in Rhabdomyosarcoma (RMS). Annual AACR meeting 2008.

Vyas, Y. M., Park, J., Kim, H. P., Wang, X., Wang, Y., Ifedigbo, E., Watkins, S. C., Ohba, M., Ryter, S. W. & Choi, A. M. (2008). Protein Kinase C-? and -? Differentially Regulate Death-Inducing Signaling Complex Formation in Cigarette Smoke Extract-Induced Apoptosis. (Vols. 180). (7), pp. 4668-4678. Journal of Immunology. PMID: 18354190.

Nayak, J. V., Teot, L. A., Vyas, Y. M., Snyderman, C. H., Toh, E. H. & Deleyiannis, F. W. (2008). Head and neck epithelioid sarcoma in a child: diagnostic dilemma and anterolateral thigh free flap reconstruction. (Vols. 72). (5), pp. 719-724. Int J Pediatr Otorhinolaryngol. PMID: 18346795.

Vyas, Y. M., Luty, W., Rodeberg, D. & Parness, J. (2007). Antiparallel segregation of Notch components in the immunological synapse directs reciprocal signaling in allogeneic Th:DC conjugates. (Vols. 179). pp. 819-829. Journal of Immunology. PMID: 17617572.

Arora, M., Chen, L., Gallagher, I., Allen, J., Vyas, Y. M., Ray, A. & Ray, P. (2006). Simvastatin promotes Th2-type responses through the induction of the chitinase family member Ym1 in dendritic cell. (Vols. 103). pp. 7777-7782. Proceedings of the National Academy of Science USA. PMID: 16682645.

Vyas, Y. M., Rodeberg, D., Parness, J. & Luty, W. (2006). Bi-directional Notch Signaling via Signal-Sending and Signal-Receiving Microdomains of the Partnered Immune Synapses during Th:DC Interaction. (Vols. 108). (11), pp. 194A-195A. BLOOD.

Chou, A., Merola, P., Wexler, L., Gorlick, R., Vyas, Y. M., Healey, J., LaQuaglia, M., Huvos, A. & Meyers, P. (2005). Treatment of Osteosarcoma at first relapse after contemporary therapy: The Memorial Sloan-Kettering Cancer Center Experience. (Vols. 104). pp. 2214-2221. Cancer. PMID: 16206297.

Vyas, Y. M., Huang, W., Ochs, H. D. & Dupont, B. (2005). The Wiskott-Aldrich Syndrome protein regulates nuclear translocation of NFAT2 and NF-?B (RelA) independently of its role in F-actin polymerization and actin cytoskeletal rearrangement. (Vols. 174). pp. 2602-2611. Journal of Immunology. PMID: 15728466.

Humblet-Baron, S., Anover, S., Kipp, K., Zhu, Q., Ye, P., Zhang, W., Ovechkina, Y., Khim, S., Astrakhan, A., Strom, T., Kohn, D., Candotti, F., Vyas, Y. M., Ochs, H., Miao, C. & Rawlings, D. (2005). Lentiviral vector-mediated gene therapy as treatment for Wiskott-Aldrich Syndrome (WAS): Pre-clinical studies in human cell lines and WASp -/- mice. (Vols. 11). (1), pp. S133. Molecular Therapy.

Vyas, Y. M., Dupont, B., Ochs, H., Huang, W. & Sisson, R. (2004). Wiskott-Aldrich Syndrome protein in NK cell regulates actin polymerization-independent nuclear translocation of NFAT2. FASEB J.

Vyas, Y. M., Huang, W., Ochs, H. & Dupont, B. (2004). Wiskott-Aldrich Syndrome protein regulates nuclear translocation of NFAT2 and NF-kB (RelA) independently of its role in F-actin polymerization and actin cytoskeletal rearrangement. XI Annual Meeting for the European Society of Immunodeficiency-October 21-24, 2004..

Vyas, Y. M., Maniar, H., Lyddane, C. E., Sadelain, M. & Dupont, B. (2004). Cognate Ligand binding to inhibitory killer cell Ig-like receptors induce co-localization with SH2-containing PTP-1 (SHP-1) and interruption of ongoing activation signals. (Vols. 173). pp. 1571-1578. Journal of Immunology. PMID: 15265884.

Vyas, Y. M., Doubrovina, E., Doubrovin, M., Vider, E., Guerrero, J., O'Reilly, R., Sisson, R. & Dupont, B. (2003). NKG2D expressing NK cells are critical in containment of MICA/B-positive human colon adenocarcinoma. (Vols. 87). pp. 77. Immunology Letters.

Vyas, Y. M., Sisson, R., O'Reilly, R. J., Rosen, M. K., Ochs, H. & Dupont, B. (2003). A Role for Wiskott-Aldrich Syndrome Protein in NK Cell Transcriptional Activation of Immune Function Genes but Not in Cytotoxic Effector Function. (Vols. 102). (11), pp. 1009. BLOOD.

Vyas, Y. M., Doubrovina, E. S., Doubrovin, M. M., Vider, E., Sisson, R. B., O'Reilly, R. J. & Dupont, B. (2003). Evasion from Natural Killer Cell Immunity by MIC expressing colon adenocarcinoma. (Vols. 171). pp. 6891-6899. Journal of Immunology. PMID: 14662896.

Vyas, Y. M., Maniar, H. & Dupont, B. (2002). Quantitative spatio-temporal analysis of cytolytic and non-cytolytic natural killer cell immune synapse. (Vols. 59). pp. 4-4 Suppl. 2. TISSUE ANTIGENS.

Koehne, G., Leiner, I., Vyas, Y. M., Williams, R. Y., Pamer, E. G. & O'Reilly, R. J. (2002). Down-regulation of effector function of EBV peptide-specific T cells isolated with MHC tetramers. (Vols. 100). (11), pp. 395. BLOOD.

Vyas, Y. M., Maniar, H. & Dupont, B. (2002). Cutting Edge: Differential segregation of the SH2-containing protein tyrosine phosphatase-1 (SHP-1) within early Natural Killer Cell Immune Synapse distinguishes non-cytolytic from cytolytic interactions. (Vols. 168). pp. 3150-3154. Journal of Immunology. PMID: 11907066.

Maniar, H., Vyas, Y. M. & Lyddane, C. (2002). Spatio-temporal segregation of lipid rafts, SHP-1 and inhibitory KIR molecules in the natural killer cell immune synapse. (Vols. 59). pp. 42-42 Suppl. 2. TISSUE ANTIGENS.

Vyas, Y. M., Maniar, H. & Dupont, B. (2002). Quantitation of distinct and sequential events that regulate the natural killer cell immune synapse. (Vols. 16). (5), pp. A1055-A155 Part 2. FASEB J.

Vyas, Y. M., Maniar, H. & Dupont, B. (2002). Visualization of signaling pathways and cortical cytoskeleton in cytolytic and non-cytolytic natural killer cell immune synapse. (Vols. 189). pp. 161-78. Immunological Reviews. PMID: 12445273.

Butros, L. J., Vyas, Y. M. & Dupont, B. (2001). Signal transduction molecules involved in murine natural killer cell interactions with the lymphoma cell lines, RMA and RMA-S. (Vols. 98). (11), pp. 74. BLOOD.

Vyas, Y. M., Maniar, H. & Lyddane, C. E. (2001). Spatial and temporal redistribution of inhibitory KIR molecules in the Natural Killer cell immune synapse. (Vols. 15). (5) FASEB J.

Doubrovina, E. S., Doubrovin, M. M., Dupont, B. & Vyas, Y. M. (2001). The in vitro upregulation of NKG2D receptor allows for the tumor specific natural killer (NK) cell immune response against the autologous colon cancer tumor. (Vols. 98). pp. 2124. BLOOD.

Vyas, Y. M., Mehta, K., Morgan, M., Butros, L., Selvakumar, A., Jung, S., Burkhardt, J. & Dupont, B. (2001). Spatial organization of signal transduction molecules in the natural killer cell immune synapse during MHC class I dependent cytolytic and non-cytolytic interactions. (Vols. 167). pp. 4358-4367. Journal of Immunology.

Vyas, Y. M., Mehta, K. & Morgan, M. (2000). NK cell immune synapse in cytolytic and non-cytolytic interactions. (Vols. 14). (6) FASEB J.

Vyas, Y. M., Butros, L. & Mehta, K. (2000). Distinctive distribution of signal transduction molecules in natural killer (NK) cell immune synapses during MHC class I dependent cytolytic versus non-cytolytic interactions. (Vols. 96). (11), pp. 3495. BLOOD.

Franco, S., Vyas, Y. M. & McKenzie, K. L. (1999). Differential upregulation of telomerase in NK (natural killer) and T lymphocytes in vitro. (Vols. 94). (10), pp. 1999. BLOOD.

Selvakumar, A., Vyas, Y. M., Steffens, U., Palanisamy, N., Chaganti, R. S. & Dupont, B. (1999). Genomic organization of two Killer cell Immunoglobulin- like receptor genes encoding KIR3DL1 molecules with three Ig-domains. (Vols. 60). pp. S147. Human Immunology.

Vyas, Y. M., Selvakumar, A. & Steffens, U. (1998). Multiple transcripts of the killer cell immunoglobulin-like receptor family, KIR3DL1 (NKB1), are expressed by NK cells of a single individual. (Vols. 92). pp. 1393. BLOOD.

Vyas, Y. M., Selvakumar, A., Steffens, U. & Dupont, B. (1998). Multiple transcripts of the killer cell immunoglobulin-like receptor family, KIR3DL1 (NKB1) are expressed by NK cells of a single individual. (Vols. 52). (6), pp. 510-519. Tissue Antigens. PMID: 9894849.

Vyas, Y. M., Selvakumar, A. & Cheung, N. K. (1998). Identification and characterization of autologous natural killer cell clones with anti-tumor reactivity in childhood stage 4 neuroblastoma. (Vols. 92). pp. 2228. BLOOD.

Steffens, U., Vyas, Y. M., Dupont, B. & Selvakumar, A. (1998). Nucleotide and amino acid sequence alignment for human killer cell inhibitory receptors (KIR). (Vols. 51). pp. 398-413. Tissue Antigens. PMID: 9583814.

Steffens, U., Selvakumar, A. & Vyas, Y. M. (1997). PCR-DNA typing of KIRs on NK cells in HLA class I homozygous and heterozygous individuals. (Vols. 55). pp. 95. HUM IMMUNOL.