Kenneth <span>Y.</span> Tsai, MD, PhD
Researcher

Kenneth Y. Tsai, MD, PhD

Academic Rank: Associate Member

Overview

The Tsai Lab has the collective goals of identifying, testing, and validating novel targets for the targeted chemoprevention and treatment of skin cancer. 

Discipline

    • Anatomic Pathology
    • Tumor Biology
    • Melanoma Research Center of Excellence
    • Chemical Biology and Molecular Medicine Program

Education & Training

    • Massachusetts Institute of Technology, PhD - Biology
    • Harvard Medical School, MD - Medicine
    • Harvard Medical School - Massachusetts General Hospital, Resident - Dermatology
    • Harvard Medical School - Beth Israel Deaconess Hospital, Fellow - Dermatopathology
Research

The focus of Dr. Tsai’s laboratory is the identification and validation of new molecularly-targeted approaches for skin cancer prevention and treatment. In contrast to melanoma, which has 27 FDA-approved therapies, the non-melanoma skin cancers, which include basal cell, squamous cell, and Merkel cell carcinomas have but two (as of early 2017), highlighting vast differences in the fundamental molecular understanding of these diseases. Following Dr. Tsai’s clinical training, he started his laboratory at MD Anderson Cancer Center, where he refined his focus on cutaneous squamous cell carcinoma (cuSCC) development. His work is centered on (1) developing an integrated genomic characterization of cuSCC development using next generation sequencing and UV-driven mouse models to identify and validate chemoprevention and therapeutic targets; (2) characterizing the roles of JNK signaling and validating JNK2 as a target in skin cancers (cuSCC and melanoma); (3) developing novel technologies to assess skin cancer risk and measure skin-based surrogate pharmacodynamic endpoints in cancer therapy. In this last area of technology development, he collaborates extensively on extramurally-funded projects with Samir Mitragotri, Ph.D. (UCSB) and Kevin Dalby, Ph.D. (UT Austin) to develop novel technologies to non-invasively sample skin for biomarker discovery and to validate additional kinase targets for cancer therapy.  Dr. Tsai’s work has been internationally recognized and he was an active member of the international melanoma TCGA Analysis Working Group. He has served as a mentor and thesis advisor to several MD/PhD and PhD graduate students, residents, and postdoctoral fellows. Most recently, he assumed the role of Section Head, Non-Melanoma Skin Cancer Research and Treatment within the Moffitt Cancer Center Donald A. Adam Melanoma and Skin Cancer Center of Excellence, where his mission is to develop and lead a premier translational research and clinical trial program for high-risk squamous cell and Merkel cell carcinomas.

Publications

  • Ku AT, Shaver TM, Rao AS, Howard JM, Rodriguez CN, Miao Q, Garcia G, Le D, Yang D, Borowiak M, Cohen DN, Chitsazzadeh V, Diwan AH, Tsai KY, Nguyen H. TCF7L1 promotes skin tumorigenesis independently of β-catenin through induction of LCN2. Elife. 2017 May;6. Pubmedid: 28467300. Pmcid: PMC5438253.
  • Fiziev P, Akdemir KC, Miller JP, Keung EZ, Samant NS, Sharma S, Natale CA, Terranova CJ, Maitituoheti M, Amin SB, Martinez-Ledesma E, Dhamdhere M, Axelrad JB, Shah A, Cheng CS, Mahadeshwar H, Seth S, Barton MC, Protopopov A, Tsai KY, Davies MA, Garcia BA, Amit I, Chin L, Ernst J, Rai K. Systematic Epigenomic Analysis Reveals Chromatin States Associated with Melanoma Progression. Cell Rep. 2017 Apr;19(4):875-889. Pubmedid: 28445736. Pmcid: PMC5473172.
  • Adelmann CH, Truong KA, Liang RJ, Bansal V, Gandee L, Saporito R, Lee W, Du L, Nicholas C, Napoli M, Mino B, South AP, Proby CM, Leigh IM, Coarfa C, Flores ER, Tsai KY. MEK Is a Therapeutic and Chemopreventative Target in Squamous Cell Carcinoma. J Invest Dermatol. 2016 Sep;136(9):1920-1924. Pubmedid: 27293029. Pmcid: PMC5303342.
  • Tsai KY. The preneoplastic genome: transcriptomic drivers of squamous cell carcinoma development. Dermatol Online J. 2016 Sep;22(9). Pubmedid: 28329662.
  • Adelmann CH, Ching G, Du L, Saporito RC, Bansal V, Pence LJ, Liang R, Lee W, Tsai KY. Comparative profiles of BRAF inhibitors: the paradox index as a predictor of clinical toxicity. Oncotarget. 2016 May;7(21):30453-30460. Pubmedid: 27028853. Pmcid: PMC5058692.
  • Feldmeyer L, Ching G, Vin H, Ma W, Bansal V, Chitsazzadeh V, Jahan-Tigh R, Chu EY, Fuller P, Maiti S, Davis RE, Cooper LJ, Tsai KY. Differential T-cell subset representation in cutaneous squamous cell carcinoma arising in immunosuppressed versus immunocompetent individuals. Exp Dermatol. 2016 Mar;25(3):245-247. Pubmedid: 26475987.
  • Napoli M, Venkatanarayan A, Raulji P, Meyers BA, Norton W, Mangala LS, Sood AK, Rodriguez-Aguayo C, Lopez-Berestein G, Vin H, Duvic M, Tetzlaff MB, Curry JL, Rook AH, Abbas HA, Coarfa C, Gunaratne PH, Tsai KY, Flores ER. ΔNp63/DGCR8-Dependent MicroRNAs Mediate Therapeutic Efficacy of HDAC Inhibitors in Cancer. Cancer Cell. 2016 Jun;29(6):874-888. Pubmedid: 27300436. Pmcid: PMC4908836.
  • Warthaka M, Adelmann CH, Kaoud TS, Edupuganti R, Yan C, Johnson WH, Ferguson S, Tavares CD, Pence LJ, Anslyn EV, Ren P, Tsai KY, Dalby KN. Quantification of a Pharmacodynamic ERK End Point in Melanoma Cell Lysates: Toward Personalized Precision Medicine. ACS Med Chem Lett. 2015 Jan;6(1):47-52. Pubmedid: 25589929. Pmcid: PMC4291693.
  • Venkatanarayan A, Raulji P, Norton W, Chakravarti D, Coarfa C, Su X, Sandur SK, Ramirez MS, Lee J, Kingsley CV, Sananikone EF, Rajapakshe K, Naff K, Parker-Thornburg J, Bankson JA, Tsai KY, Gunaratne PH, Flores ER. IAPP-driven metabolic reprogramming induces regression of p53-deficient tumours in vivo. Nature. 2015 Jan;517(7536):626-630. Pubmedid: 25409149. Pmcid: PMC4312210.
  • Maresso KC, Tsai KY, Brown PH, Szabo E, Lippman S, Hawk ET. Molecular cancer prevention: Current status and future directions. CA-Cancer J Clin. 2015 Dec;65(5):345-383. Pubmedid: 26284997. Pmcid: PMC4820069.
  • Amaravadi RK, Hamilton KE, Ma X, Piao S, Portillo AD, Nathanson KL, Carlino MS, Long GV, Puzanov I, Xu X, Morrissette JJ, Tsai KY, Flaherty KT, Sosman JA, Goodman GR, McArthur GA, Rustgi AK, Metz DC, Schuchter LM, Chapman PB, Sepulveda AR. Multiple Gastrointestinal Polyps in Patients Treated with BRAF Inhibitors. Clin Cancer Res. 2015 Dec;21(23):5215-5221. Pubmedid: 26202952. Pmcid: PMC4668213.
  • Watson IR, Li L, Cabeceiras PK, Mahdavi M, Gutschner T, Genovese G, Wang G, Fang Z, Tepper JM, Stemke-Hale K, Tsai KY, Davies MA, Mills GB, Chin L. The RAC1 P29S hotspot mutation in melanoma confers resistance to pharmacological inhibition of RAF. Cancer Res. 2014 Sep;74(17):4845-4852. Pubmedid: 25056119. Pmcid: PMC4167745.
  • Fowler NH, Davis RE, Rawal S, Nastoupil L, Hagemeister FB, McLaughlin P, Kwak LW, Romaguera JE, Fanale MA, Fayad LE, Westin JR, Shah J, Orlowski RZ, Wang M, Turturro F, Oki Y, Claret LC, Feng L, Baladandayuthapani V, Muzzafar T, Tsai KY, Samaniego F, Neelapu SS. Safety and activity of lenalidomide and rituximab in untreated indolent lymphoma: an open-label, phase 2 trial. Lancet Oncol. 2014 Nov;15(12):1311-1318. Pubmedid: 25439689. Pmcid: PMC4370362.
  • Pattanaprichakul P, Tetzlaff MT, Lapolla WJ, Torres-Cabala CA, Duvic M, Prieto VG, Tsai KY, Curry JL. Sweet syndrome following vemurafenib therapy for recurrent cholangiocarcinoma. J Cutan Pathol. 2014 Mar;41(3):326-328. Pubmedid: 24372055.
  • Curry JL, Torres-Cabala CA, Kim KB, Tetzlaff MT, Duvic M, Tsai KY, Hong DS, Prieto VG. Dermatologic toxicities to targeted cancer therapy: shared clinical and histologic adverse skin reactions. Int J Dermatol. 2014 Mar;53(3):376-384. Pubmedid: 23879247.
  • Curry JL, Tetzlaff MT, Nicholson K, Duvic M, Kim KB, Tsai KY, Hwu WJ, Hong DS, Prieto VG, Torres-Cabala CA. Histological features associated with vemurafenib-induced skin toxicities: examination of 141 cutaneous lesions biopsied during therapy. Am J Dermatopathxxx. 2014 Jul;36(7):557-561. Pubmedid: 24950418.
  • Ma Q, Li D, Carreño R, Patenia R, Tsai KY, Xydes-Smith M, Alousi AM, Champlin RE, Sale GE, Afshar-Kharghan V. Complement component C3 mediates Th1/Th17 polarization in human T-cell activation and cutaneous GVHD. Bone Marrow Transplant. 2014 Jul;49(7):972-976. Pubmedid: 24777193. Pmcid: PMC4410869.
  • Vin H, Ching G, Ojeda SS, Adelmann CH, Chitsazzadeh V, Dwyer DW, Ma H, Ehrenreiter K, Baccarini M, Ruggieri R, Curry JL, Ciurea AM, Duvic M, Busaidy NL, Tannir NM, Tsai KY. Sorafenib suppresses JNK-dependent apoptosis through inhibition of ZAK. Mol Cancer Ther. 2014 Jan;13(1):221-229. Pubmedid: 24170769. Pmcid: PMC4366425.
  • Pickering CR, Zhou JH, Lee JJ, Drummond JA, Peng SA, Saade RE, Tsai KY, Curry JL, Tetzlaff MT, Lai SY, Yu J, Muzny DM, Doddapaneni H, Shinbrot E, Covington KR, Zhang J, Seth S, Caulin C, Clayman GL, El-Naggar AK, Gibbs RA, Weber RS, Myers JN, Wheeler DA, Frederick MJ. Mutational landscape of aggressive cutaneous squamous cell carcinoma. Clin Cancer Res. 2014 Dec;20(24):6582-6592. Pubmedid: 25303977. Pmcid: PMC4367811.
  • Tsai KY, Nowroozi S, Kim KB. Drug safety evaluation of vemurafenib in the treatment of melanoma. Expert Opin Drug Saf. 2013 Sep;12(5):767-775. Pubmedid: 23800008.
  • Hwang BH, Tsai KY, Mitragotri S. Optimized lysis buffer reagents for solubilization and preservation of proteins from cells and tissues. Drug Deliv Transl Res. 2013 Oct;3(5):428-436. Pubmedid: 25788351.
  • Vin H, Ojeda SS, Ching G, Leung ML, Chitsazzadeh V, Dwyer DW, Adelmann CH, Restrepo M, Richards KN, Stewart LR, Du L, Ferguson SB, Chakravarti D, Ehrenreiter K, Baccarini M, Ruggieri R, Curry JL, Kim KB, Ciurea AM, Duvic M, Prieto VG, Ullrich SE, Dalby KN, Flores ER, Tsai KY. BRAF inhibitors suppress apoptosis through off-target inhibition of JNK signaling. Elife. 2013 Nov;2:e00969. Pubmedid: 24192036. Pmcid: PMC3814616.
  • Paliwal S, Hwang BH, Tsai KY, Mitragotri S. Diagnostic opportunities based on skin biomarkers. Eur J Pharm Sci. 2013 Dec;50(5):546-556. Pubmedid: 23159445.
  • Hwang BH, Doshi N, Tsai KY, Mitragotri S. A reagent to facilitate protein recovery from cells and tissues. Drug Deliv Transl Res. 2012 Oct;2(5):297-304. Pubmedid: 25787172.
  • Su X, Gi YJ, Chakravarti D, Chan IL, Zhang A, Xia X, Tsai KY, Flores ER. TAp63 is a master transcriptional regulator of lipid and glucose metabolism. Cell Metab. 2012 Oct;16(4):511-525. Pubmedid: 23040072. Pmcid: PMC3483083.
  • Matthias N, Lockworth CR, Zhang F, Lee MH, Yeung SC, Tsai KY, Hamir AN. Multiple cystic sweat gland tumors in transgenic mice. Comp Med. 2012 Feb;62(1):27-30. Pubmedid: 22330648. Pmcid: PMC3276389.
  • Rangwala S, Tsai KY. Roles of the immune system in skin cancer. Br J Dermatol. 2011 Nov;165(5):953-965. Pubmedid: 21729024. Pmcid: PMC3197980.
  • Silapunt S, Jordon RE, Piao Y, Tsai KY. Kaposi sarcoma presenting as a cutaneous horn. J Am Acad Dermatol. 2011 Feb;64(2):447-448. Pubmedid: 21238839.
  • Bergman H, Tsai KY, Seo SJ, Kvedar JC, Watson AJ. Remote assessment of acne: the use of acne grading tools to evaluate digital skin images. Telemed E-Health. 2009 Jun;15(5):426-430. Pubmedid: 19548822.
  • Su X, Paris M, Gi YJ, Tsai KY, Cho MS, Lin YL, Biernaskie JA, Sinha S, Prives C, Pevny LH, Miller FD, Flores ER. TAp63 prevents premature aging by promoting adult stem cell maintenance. Cell Stem Cell. 2009 Jul;5(1):64-75. Pubmedid: 19570515. Pmcid: PMC3418222.
  • Yang G, Thieu K, Tsai KY, Piris A, Udayakumar D, Njauw CN, Ramoni MF, Tsao H. Dynamic gene expression analysis links melanocyte growth arrest with nevogenesis. Cancer Res. 2009 Dec;69(23):9029-9037. Pubmedid: 19903842.
  • Tucker JD, Shah S, Jarell AD, Tsai KY, Zembowicz A, Kroshinsky D. Lues maligna in early HIV infection case report and review of the literature. Sex Transm Dis. 2009 Aug;36(8):512-514. Pubmedid: 19455078.
  • Davis TL, Mandal RV, Bevona C, Tsai KY, Moschella SL, Staszewski R, Zembowicz A. Collagenous vasculopathy: a report of three cases. J Cutan Pathol. 2008 Oct;35(10):967-970. Pubmedid: 18537865.
  • Tsai KY. Systemic adjuvant therapy for patients with high-risk melanoma. Arch Dermatol. 2007 Jun;143(6):779-782. Pubmedid: 17576946.
  • Niendorf KB, Goggins W, Yang G, Tsai KY, Shennan M, Bell DW, Sober AJ, Hogg D, Tsao H. MELPREDICT: a logistic regression model to estimate CDKN2A carrier probability. J Med Genet. 2006 Jun;43(6):501-506. Pubmedid: 16169933. Pmcid: PMC2564534.
  • Tsai KY. Evidence-based medicine: do we use guidelines or mindlines? Commentary on: Evidence-based guidelines or collectively constructed "mindlines?" ethnographic study of knowledge management in primary care. Gabbay J, le May G BMJ. 2004;329:1013. Arch Dermatol. 2005 Jun;141(6):773-774. Pubmedid: 15967926.
  • Tsai KY, MacPherson D, Rubinson DA, Crowley D, Jacks T. ARF is not required for apoptosis in Rb mutant mouse embryos. Curr Biol. 2002 Jan;12(2):159-163. Pubmedid: 11818069.
  • Tsai KY, MacPherson D, Rubinson DA, Nikitin AY, Bronson R, Mercer KL, Crowley D, Jacks T. ARF mutation accelerates pituitary tumor development in Rb+/- mice. Proc Natl Acad Sci U S A. 2002 Dec;99(26):16865-16870. Pubmedid: 12486224. Pmcid: PMC139235.
  • Flores ER, Tsai KY, Crowley D, Sengupta S, Yang A, McKeon F, Jacks T. p63 and p73 are required for p53-dependent apoptosis in response to DNA damage. Nature. 2002 Apr;416(6880):560-564. Pubmedid: 11932750.
  • Geng Y, Yu Q, Whoriskey W, Dick F, Tsai KY, Ford HL, Biswas DK, Pardee AB, Amati B, Jacks T, Richardson A, Dyson N, Sicinski P. Expression of cyclins E1 and E2 during mouse development and in neoplasia. Proc Natl Acad Sci U S A. 2001 Nov;98(23):13138-13143. Pubmedid: 11687642. Pmcid: PMC60837.
  • Boyd SD, Tsai KY, Jacks T. An intact HDM2 RING-finger domain is required for nuclear exclusion of p53. Nat Cell Biol. 2000 Sep;2(9):563-568. Pubmedid: 10980695.
  • Alenghat FJ, Fabry B, Tsai KY, Goldmann WH, Ingber DE. Analysis of cell mechanics in single vinculin-deficient cells using a magnetic tweezer. Biochem Bioph Res Co. 2000 Oct;277(1):93-99. Pubmedid: 11027646.
  • Irwin M, Marin MC, Phillips AC, Seelan RS, Smith DI, Liu W, Flores ER, Tsai KY, Jacks T, Vousden KH, Kaelin WG. Role for the p53 homologue p73 in E2F-1-induced apoptosis. Nature. 2000 Oct;407(6804):645-648. Pubmedid: 11034215.
  • Tsai KY, Hu Y, Macleod KF, Crowley D, Yamasaki L, Jacks T. Mutation of E2f-1 suppresses apoptosis and inappropriate S phase entry and extends survival of Rb-deficient mouse embryos. Mol Cell. 1998 Sep;2(3):293-304. Pubmedid: 9774968.
  • Lee KM, Tsai KY, Wang N, Ingber DE. Extracellular matrix and pulmonary hypertension: control of vascular smooth muscle cell contractility. Am J Physiol. 1998 Jan;274(1 Pt 2):H76-H82. Pubmedid: 9458854.
  • Carnevale NT, Tsai KY, Claiborne BJ, Brown TH. Comparative electrotonic analysis of three classes of rat hippocampal neurons. J Neurophysiol. 1997 Aug;78(2):703-720. Pubmedid: 9307106.
  • Hoffmann RE, Buchsbaum MS, Jensen RV, Guich SM, Tsai K, Nuechterlein KH. Dimensional complexity of EEG waveforms in neuroleptic-free schizophrenic patients and normal control subjects. J Neuropsych Clin N. 1996;8(4):436-441. Pubmedid: 9116481.
  • Mays R, Curry J, Kim K, Tsai K, Arora A, Khan F, Ramirez-Fort M, Ciurea A. Eruptive squamous cell carcinomas after vemurafenib therapy. J Cutan Med Surg. 17(6):419-422. Pubmedid: 24138980.