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Radiation and Cancer Biology
Nyati Lab

Nyati_MukeshMukesh Nyati, PhD
Associate Professor of Radiation Oncology

Professor Nyati received his Ph.D. from the University of Rajasthan, Jaipur, India and post-doctoral training in Dr. Ted Lawrence’s laboratory at the University of Michigan.  Dr. Nyati has been working on basic, translational as well as clinical aspect of EGFR signaling. His research is continued to be funded by NIH.  In the laboratory, Dr. Nyati is working on developing novel therapeutic agents including cell permeable peptides and their structural analogues to degrade EGFR. The main objective of this work is to sensitize tyrosine kinase inhibitor (TKI) resistant EGFR-driven tumors by promoting tumor specific EGFR degradation through blocking EGFR dimers and EGFR Hsp90 interactions.  Dr. Nyati is also working in collaboration with both basic scientist and clinicians in the head and neck SPORE program at the University of Michigan to discover novel biomarkers of “response” to molecularly targeted therapy.  The long- term goal of this research is to identify patients who are likely to respond to molecularly targeted therapy in combination with chemotherapy and/or radiotherapy early in the course of treatment so that the combination regimen is optimized.

Faculty Appointment: Associate Professor, Department of Radiation Oncology 
Specialty: Radiation Oncology
Research Interests: Signal transduction, protein degradation, radiation sensitization and experimental therapeutics. 
Degree: Ph.D., 1996, University of Rajasthan, Jaipur, INDIA
Added Qualification:  1997, Ph.D.
Faculty Appointment: Date:1/7/1999 
Contact: nyati@umich.edu or nyati@med.umich.edu

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Publications

  1. Gupta RR, Dev PK, Sharma ML, Rajoria CM, Gupta A, Nyati M. Anticancer activities of 2,3-dihydro-1,4-benzothiazines, and of their 4-(N-alkyl amides) and 4-(N-alkyl N-nitrosoamides). Anticancer Drugs. 1993;4:589-92.
  2. Nyati MK, Rajoria CM, Gupta RR, Dev PK. Evaluation of certain ureas and nitrosoureas of 2,3-dihydro-1,4-benzothiazines against Sarcoma-180 solid tumors in vivo. Anticancer Drugs. 1995;6:693-6.
  3. Nyati MK, Rai D, Gupta RR, Dev PK. Development of differential cytotoxic compounds containing nitrosourea and benzothiazine nucleus. In Vivo. 1997;11:95-9.
  4. Kievit E, Nyati MK, Ng E, Stegman LD, Parsels J, Ross BD, Rehemtulla A, Lawrence TS. Yeast cytosine deaminase improves radiosensitization and bystander effect by 5-fluorocytosine of human colorectal cancer xenografts. Cancer Res. 2000;60:6649-55.
  5. Sreekumar A, Nyati MK, Varambally S, Barrette TR, Ghosh D, Lawrence TS, Chinnaiyan AM. Profiling of cancer cells using protein microarrays: discovery of novel radiation-regulated proteins. Cancer Res. 2001;61:7585-93.
  6. Lawrence TS, Nyati MK. Small-molecule tyrosine kinase inhibitors as radiosensitizers. Semin Radiat Oncol. 2002;12:33-6.
  7. Nyati MK, Sreekumar A, Li S, Zhang M, Rynkiewicz SD, Chinnaiyan AM, Rehemtulla A, Lawrence TS. High and selective expression of yeast cytosine deaminase under a carcinoembryonic antigen promoter-enhancer. Cancer Res. 2002;62:2337-42.
  8. Nyati MK, Symon Z, Kievit E, Dornfeld KJ, Rynkiewicz SD, Ross BD, Rehemtulla A, Lawrence TS. The potential of 5-fluorocytosine/cytosine deaminase enzyme prodrug gene therapy in an intrahepatic colon cancer model. Gene Ther. 2002;9:844-9.
  9. Zhang M, Li S, Nyati MK, DeRemer S, Parsels J, Rehemtulla A, Ensminger WD, Lawrence TS. Regional delivery and selective expression of a high-activity yeast cytosine deaminase in an intrahepatic colon cancer model. Cancer Res. 2003;63:658-63.
  10. Nyati MK, Maheshwari D, Hanasoge S, Sreekumar A, Rynkiewicz SD, Chinnaiyan AM, Leopold WR, Ethier SP, Lawrence TS. Radiosensitization by pan ErbB inhibitor CI-1033 in vitro and in vivo. Clin Cancer Res. 2004;10:691-700.
  11. Nyati MK, Lawrence TS. Hitting the target: measuring EGFR response to tyrosine kinase inhibitors. Cancer Biol Ther. 2005;4:1387-8.
  12. Chun PY, Feng FY, Scheurer AM, Davis MA, Lawrence TS, Nyati MK. Synergistic effects of gemcitabine and gefitinib in the treatment of head and neck carcinoma. Cancer Res. 2006;66:981-8.
  13. Nyati MK, Feng FY, Kanade VD, Nayak R. Chloroquine treatment increases detection of 5-fluorouracil-induced apoptosis index in vivo. Mol Imaging. 2006;5:148-52.
  14. Nyati MK, Feng FY, Maheshwari D, Varambally S, Zielske SP, Ahsan A, Chun PY, Arora VA, Davis MA, Jung M, Ljungman M, Canman CE, Chinnaiyan AM, Lawrence TS. Ataxia telangiectasia mutated down-regulates phospho-extracellular signal-regulated kinase 1/2 via activation of MKP-1 in response to radiation. Cancer Res. 2006;66:11554-9.
  15. Nyati MK, Morgan MA, Feng FY, Lawrence TS. Integration of EGFR inhibitors with radiochemotherapy. Nat Rev Cancer. 2006;6:876-85.
  16. Feng FY, Lopez CA, Normolle DP, Varambally S, Li X, Chun PY, Davis MA, Lawrence TS, Nyati MK. Effect of epidermal growth factor receptor inhibitor class in the treatment of head and neck cancer with concurrent radiochemotherapy in vivo. Clin Cancer Res. 2007;13:2512-8.
  17. Feng FY, Varambally S, Tomlins SA, Chun PY, Lopez CA, Li X, Davis MA, Chinnaiyan AM, Lawrence TS, Nyati MK. Role of epidermal growth factor receptor degradation in gemcitabine-mediated cytotoxicity. Oncogene. 2007;26:3431-9.
  18. Lopez CA, Feng FY, Herman JM, Nyati MK, Lawrence TS, Ljungman M. Phenylbutyrate sensitizes human glioblastoma cells lacking wild-type p53 function to ionizing radiation. Int J Radiat Oncol Biol Phys. 2007;69:214-20.
  19. Ahsan A, Hiniker SM, Davis MA, Lawrence TS, Nyati MK. Role of cell cycle in epidermal growth factor receptor inhibitor-mediated radiosensitization. Cancer Res. 2009;69:5108-14.
  20. Mani RS, Tomlins SA, Callahan K, Ghosh A, Nyati MK, Varambally S, Palanisamy N, Chinnaiyan AM. Induced chromosomal proximity and gene fusions in prostate cancer. Science. 2009;326:1230.
  21. Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RJ, Li Y, Nyati MK, Ahsan A, Kalyana-Sundaram S, Han B, Cao X, Byun J, Omenn GS, Ghosh D, Pennathur S, Alexander DC, Berger A, Shuster JR, Wei JT, Varambally S, Beecher C, Chinnaiyan AM. Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature. 2009;457:910-4.
  22. Ahsan A, Hiniker SM, Ramanand SG, Nyati S, Hegde A, Helman A, Menawat R, Bhojani MS, Lawrence TS, Nyati MK. Role of epidermal growth factor receptor degradation in cisplatin-induced cytotoxicity in head and neck cancer. Cancer Res. 2010;70:2862-9.
  23. Mierzwa ML, Nyati MK, Morgan MA, Lawrence TS. Recent advances in combined modality therapy. Oncologist. 2010;15:372-81.
  24. Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RJ, Li Y, Nyati MK, Ahsan A, Kalyana-Sundaram S, Han B, Cao X, Byun J, Omenn GS, Ghoshd D, Pennathur S, Alexander DC, Berger A, Shuster JR, Wei JT, Varambally S, Beecher C, Chinnaiyan AM. Re: Florian Jentzmik, Carsten Stephan, Kurt Miller, et al. Sarcosine in urine after digital rectal examination fails as a marker in prostate cancer detection and identification of aggressive tumours. Eur Urol 2010;58:12-8. Eur Urol. 2010;58:e29-30; author reply e1-2.
  25. Argiris A, Duffy AG, Kummar S, Simone NL, Arai Y, Kim SW, Rudy SF, Kannabiran VR, Yang X, Jang M, Chen Z, Suksta N, Cooley-Zgela T, Ramanand SG, Ahsan A, Nyati MK, Wright JJ, Van Waes C. Early tumor progression associated with enhanced EGFR signaling with bortezomib, cetuximab, and radiotherapy for head and neck cancer. Clin Cancer Res. 2011;17:5755-64.
  26. Bhojani MS, Nyati MK, Zhao L, Normolle DP, Ross BD, Lawrence TS, Rehemtulla A. Molecular imaging of akt enables early prediction of response to molecular targeted therapy. Transl Oncol. 2011;4:122-5.
  27. Khan AP, Contessa JN, Nyati MK, Ross BD, Rehemtulla A. Molecular imaging of epidermal growth factor receptor kinase activity. Anal Biochem. 2011;417:57-64.
  28. Nyati S, Schinske K, Ray D, Nyati MK, Ross BD, Rehemtulla A. Molecular imaging of TGFbeta-induced Smad2/3 phosphorylation reveals a role for receptor tyrosine kinases in modulating TGFbeta signaling. Clin Cancer Res. 2011;17:7424-39.
  29. Ray D, Ahsan A, Helman A, Chen G, Hegde A, Gurjar SR, Zhao L, Kiyokawa H, Beer DG, Lawrence TS, Nyati MK. Regulation of EGFR protein stability by the HECT-type ubiquitin ligase SMURF2. Neoplasia. 2011;13:570-8.
  30. Ahsan A, Ramanand SG, Whitehead C, Hiniker SM, Rehemtulla A, Pratt WB, Jolly S, Gouveia C, Truong K, Van Waes C, Ray D, Lawrence TS, Nyati MK. Wild-type EGFR is stabilized by direct interaction with HSP90 in cancer cells and tumors. Neoplasia. 2012;14:670-7.
  31. Wang R, Asangani IA, Chakravarthi BV, Ateeq B, Lonigro RJ, Cao Q, Mani RS, Camacho DF, McGregor N, Schumann TE, Jing X, Menawat R, Tomlins SA, Zheng H, Otte AP, Mehra R, Siddiqui J, Dhanasekaran SM, Nyati MK, Pienta KJ, Palanisamy N, Kunju LP, Rubin MA, Chinnaiyan AM, Varambally S. Role of transcriptional corepressor CtBP1 in prostate cancer progression. Neoplasia. 2012;14:905-14.
  32. Ahsan A, Ray D, Ramanand SG, Hegde A, Whitehead C, Rehemtulla A, Morishima Y, Pratt WB, Osawa Y, Lawrence TS, Nyati MK. Destabilization of the epidermal growth factor receptor (EGFR) by a peptide that inhibits EGFR binding to heat shock protein 90 and receptor dimerization. J Biol Chem. 2013;288:26879-86.
  33. Ray D, Shukla S, Allam US, Helman A, Ramanand SG, Tran L, Bassetti M, Krishnamurthy PM, Rumschlag M, Paulsen M, Sun L, Shanley TP, Ljungman M, Nyati MK, Zhang M, Lawrence TS. Tristetraprolin mediates radiation-induced TNF-alpha production in lung macrophages. PLoS One. 2013;8:e57290.
  34. Tsien CI, Nyati MK, Ahsan A, Ramanand SG, Chepeha DB, Worden FP, Helman JI, D'Silva N, Bradford CR, Wolf GT, Lawrence TS, Eisbruch A. Effect of erlotinib on epidermal growth factor receptor and downstream signaling in oral cavity squamous cell carcinoma. Head Neck. 2013;35:1323-30.


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