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Kenneth Y. Tsai, M.D., Ph.D.

Present Title & Affiliation

Primary Appointment

Assistant Professor, Department of Dermatology, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX

Dual/Joint/Adjunct Appointment

Assistant Professor, Department of Translational Molecular Pathology, Division of Pathology/Lab Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX
Regular Faculty Member, University of Texas Graduate School of Biomedical Sciences, Houston, TX

Research Interests

Skin cancer is the most common group of malignancies in humans.


Our research is focused on the mechanisms of skin cancer development andprogression. For our studies, we utilize a combination of cell culture, in-vivo mouse models and human skinsamples to explore four primary areas:

 

1)              Genomic Analysis of Cutaneous Squamous Cell Carcinoma Progression

 

Cutaneous squamous cell carcinoma (cSCC) is the 2nd most common skin cancer. It has the best established clinical and histologic progression sequence of all skin cancers, most often arising in UV-irradiated skin, progressingto the preneoplastic actinic keratosis (AK), and then to invasive carcinoma (cSCC). We have undertaken a comprehensive integrated genomic approach to understand the molecular drivers of this progression sequence so as to identify molecular biomarkers that predict risk of progression and to identify pathways and genes. We are interested in addressing the following questions: (1) What are the major driver pathways of cSCC progression ?; (2)  Which proteins or RNAs may be used as biomarkers of risk of progression and which may be used as targets for molecularly-driven chemoprevention ?


https://www.youtube.com/watch?v=1MaQMs4--TA


2)             Interactions of MAP Kinase Pathways in Targeted Therapy for Melanoma

 

Metastatic melanoma is an incurable cancer that often arises in the skin, but recent developments in targeted therapy and immune therapy offerimportant survival benefits. We have recently discovered a novel and unexpectedninteraction between targeted therapies for melanoma (vemurafenib / PLX4720) and stress-activated MAP kinase pathways. This has important clinical implications for combining these therapies with other modalities that induce apoptosis and may also explain in part some of the adverse reactions to these drugs,  including the development of squamous cell carcinomas. We are interested in answering the following questions: (1) What are the mechanisms by which these drugs impact apoptosis and autophagy pathways ?; (2) How do the effects on these pathways affect response of tumor cells to therapy or explain adverse effects of these drugs ?

 

3)           Establishment of Skin as a Surrogate Biomarker in Targeted Therapies

 

Since the advent of imatinib, molecularly-targeted therapy has revolutionized cancer treatment. There are now several rationally-designed antibody-based and small molecule inhibitors that have produced impressive clinical responses. Despite this, one fundamental problemis the inability to predict who will respond and who will not, a critical determinant of the ability to practice  precision medicine. How can the patients most likely to respond be identified and optimally treated with appropriate drugs ? How can mechanisms of acquired resistance be predicted ? Can off-target effects be predicted and managed proactively ?

 

This presents an opportunity to establish skin as a surrogate biomarker of drug efficacy in vivo. We have been actively involved in the development of a novel proprietary reagent that enables the solubilization of tissue with preservation of protein and nucleic acids. We have already validated its safety and functionality in mouse skin and will soon establish safety and efficacy of sample recovery and skin solubilization inhumans. Our plan is to establish this technology as a means of profiling epidermal cells in vivo. We are interested in addressing the following questions: (1) Can gene expression and phospho-protein profiles of skin be used as biomarkers for targeted therapies or drugs with narrow therapeutic indices ?; (2) Can this non-invasive technology optimize drug dosing, safety, and monitoring ?


4)             The Immunology of Skin Cancer

 

The immune status of patients and model organisms dramatically impacts the development and progression of many cancers, in particular skin cancers such as squamous cell carcinoma (SCC). Organ transplant recipients are at extremely high risk for these cancers, which are not only more frequent, but more lethal in these immunosuppressed individuals. We are interested in answering the following questions: (1) How do immune cell subsets such as regulatory T-cells or cytotoxic T-cells contribute to tumor progression and tumor control ?; (2) How do tumors escape immune destruction or adapt to immune pressure ?

 

Office Address

The University of Texas MD Anderson Cancer Center Departments of Dermatology and Immunology
7455 Fannin St., Unit 907
Unit Number: 907
Houston, TX 77054
Room Number: SCR1.2021
Phone: 713-563-1943
Fax: 713-563-0110
Email: kytsai@mdanderson.org

Education & Training

Degree-Granting Education

2003 Harvard Medical School, Boston, MA, MD, Medicine
2001 Massachusetts Institute of Technology, Cambridge, MA, PHD, Biology
1993 Yale College, New Haven, CT, BS, Applied Physics

Postgraduate Training

7/2007-6/2008 Clinical Fellowship, Dermatopathology, Harvard Medical School - Beth Israel Deaconess Hospital, Boston, MA
7/2004-6/2007 Clinical Residency, Dermatology, Harvard Medical School - Massachusetts General Hospital, Boston, MA
7/2003-6/2004 Clinical Internship, Internal Medicine, Massachusetts General Hospital, Boston, MA

Board Certifications

9/2008 American Boards of Dermatology & Pathology - Dermatopathology
8/2007 American Board of Dermatology - Dermatology

Honors and Awards

2013-2015 AACR Landon Foundation INNOVATOR Award, American Association for Cancer Research
2012-2014 Cyrus Research Scholar Award, Cyrus Family Foundation
2006-2007 Chief Resident, Dermatology, Harvard Medical School - Massachusetts General Hospital
2000 David Koch Foundation Graduate Fellowship, Massachusetts Institute of Technology
1994-2003 Medical Scientist Training Program, National Institutes of Health

Professional Memberships

American Academy of Dermatology, Schaumberg, IL
Fellow, 7/2008-present
American Academy of Dermatology, Schaumberg, IL
Basic Science Curriculum Committee, 12/2007
American Joint Committee on Cancer (AJCC) - Non-Melanoma Skin Expert Panel
Member, 2/2014-present
American Society of Clinical Oncology, Alexandria, VA
Member, 10/2011-present
Society for Investigative Dermatology, Cleveland, OH
Member, 7/2009-present

Selected Publications

Peer-Reviewed Original Research Articles

1. Tsai KY, Carnevale NT, Claiborne BJ, Brown TH. Efficient mapping from neuroanatomical to electrotonic space. Network 5(1):21-46, 2/1994.
2. Tsai KY, Carnevale NT, Brown TH. Hebbian learning is jointly controlled by electrotonic and input structure. Network 5(1):1-19, 2/1994.
3. Hoffman RE, Buchsbaum MS, Jensen RV, Guich SM, Tsai KY, Neuchterlein KH. Dimensional complexity of EEG waveforms in neuroleptic-free schizophrenics and normal controls. J Neuropsych Clin Neurosci 8:436-441, 1996.
4. Carnevale NT, Tsai KY, Claiborne BJ, Brown TH. Comparative electrotonic analysis of three classes of rat hippocampal neurons. J Neurophysiol 78(2):703-20, 8/1997. PMID: 9307106.
5. Lee KM, Tsai KY, Wang N, Ingber DE. Extracellular matrix and pulmonary hypertension: control of vascular smooth muscle cell contractility. Am J Physiol 274(1 Pt 2):H76-82, 1/1998. PMID: 9458854.
6. 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 2(3):293-304, 9/1998. PMID: 9774968.
7. Alenghat FJ, Fabry B, Tsai KY, Goldmann WH, Ingber DE. Analysis of cell mechanics in single vinculin-deficient cells using a magnetic tweezer. Biochem Biophys Res Commun 277(1):93-9, 10/14/2000. PMID: 11027646.
8. 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 407(6804):645-8, 10/5/2000. PMID: 11034215.
9. Boyd SD, Tsai KY, Jacks T. An intact HDM2 RING-finger domain is required for nuclear exclusion of p53. Nat Cell Biol 2(9):563-8, 9/2000. PMID: 10980695.
10. 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 98(23):13138-43, 11/6/2001. PMID: 11687642.
11. Tsai KY, MacPherson D, Rubinson DA, Crowley D, Jacks T. ARF is not required for apoptosis in Rb mutant mouse embryos. Curr Biol 12(2):159-63, 1/22/2002. PMID: 11818069.
12. 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 416(6880):560-4, 4/4/2002. PMID: 11932750.
13. 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 99(26):16865-70, 12/24/2002. PMID: 12486224.
14. Tsai KY, Tsao H. The genetics of skin cancer. Am J Med Genet C Semin Med Genet 131C(1):82-92, 11/15/2004. PMID: 15468170.
15. 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 141(6):773-4, 6/2005. PMID: 15967926.
16. 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 43(6):501-6, 6/2006. PMID: 16169933.
17. Tsai KY, Tsao H. Primer on the human genome. J Am Acad Dermatol 56(5):719-35, 5/2007. PMID: 17437886.
18. Tsai KY. Systemic adjuvant therapy for patients with high-risk melanoma. Arch Dermatol 143(6):779-82, 6/2007. PMID: 17576946.
19. Tsai KY, Brenn T, Werchniak AE. Nodular presentation of secondary syphilis. J Am Acad Dermatol 57(2 Suppl):S57-8, 8/2007. PMID: 17637381.
20. Davis TL, Mandal RV, Bevona C, Tsai KY, Moschella SL, Staszewski R, Zembowicz A. Collagenous vasculopathy: a report of three cases. J Cutan Pathol 35(10):967-70, 6/4/2008. PMID: 18537865.
21. 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. e-Pub 5/2009. PMID: 19455078.
22. 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 J E Health 15(5):426-30, 6/2009. PMID: 19548822.
23. 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 5(1):64-75, 7/2009. PMID: 19570515.
24. Yang G, Thieu K, Tsai KY, Piris A, Udayakumar D, Njauw C-NJ, Ramoni M, Tsao H. Dynamic Gene Expression Analysis Links Melanocyte Growth Arrest with Nevogenesis. Cancer Res 69(23):9029-37, 12/2009. e-Pub 11/2009. PMID: 19903842.
25. Silapunt S, Jordon RE, Piao Y, Tsai KY. Kaposi sarcoma presenting as a cutaneous horn. J Am Acad Dermatol 64(2):447-8, 2/2011. PMID: 21238839.
26. Matthias N, Lockworth CR, Zhang F, Lee MH, Yeung SC, Tsai KY, Hamir AN. Multiple cystic sweat gland tumors in transgenic mice. Comp Med 62(1):27-30, 2/2012. PMCID: PMC3276389.
27. Rangwala S, Tsai KY. Roles of the immune system in skin cancer. Br J Dermatol 165(5):953-65, 11/2011. PMCID: PMC3197980.
28. 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 16(4):511-25, 10/3/2012. PMCID: PMC3483083.
29. Paliwal S, Hwang BH, Tsai KY, Mitragotri S. Diagnostic opportunities based on skin biomarkers. Eur J Pharm Sci 50(5):546-56, 12/18/2013. e-Pub 11/15/2012. PMID: 23159445.
30. Hwang BH, Doshi N, Tsai KY, MItragotri S. A Reagent to Facilitate Protein Recovery from Cells and Tissues. Drug Deliv Transl Res 2(5):297, 10/2012.
31. Hwang BH, Tsai KY, Mitragotri S. Optimized lysis buffer reagents for solubilization and preservation of proteins from cells and tissues. Drug Deliv and Transl Res 3(5):428, 1/2013.
32. Tsai KY, Nowroozi S, Kim KB. Drug safety evaluation of vemurafenib in the treatment of melanoma. Expert Opin Drug Saf 12(5):767-75, 9/2013. e-Pub 6/26/2013. PMID: 23800008.
33. 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 53(3):376-84, 3/2014. e-Pub 7/24/2013. PMID: 23879247.
34. 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 13(1):221-229, 1/2014. e-Pub 10/29/2013. PMID: 24170769.
35. 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 2(0):e00969, 2013. e-Pub 11/5/2013. PMCID: PMC3814616.
36. 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 41(3):326-8, 3/2014. e-Pub 12/24/2013. PMID: 24372055.
37. Chakravarti D, Su X, Cho MS, Bui NH, Coarfa C, Venkatanarayan A, Benham AL, Flores González RE, Alana J, Xiao W, Leung ML, Vin H, Chan IL, Aquino A, Müller N, Wang H, Cooney AJ, Parker-Thornburg J, Tsai KY, Gunaratne PH, Flores ER. Induced multipotency in adult keratinocytes through down-regulation of ?Np63 or DGCR8. Proc Natl Acad Sci U S A 111(5):E572-81, 2/4/2014. e-Pub 1/21/2014. PMCID: PMC3918754.
38. 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 49(7):972-6, 7/2014. e-Pub 4/28/2014. PMID: 24777193.
39. 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 Dermatopathol 36(7):557-61, 7/2014. PMID: 24950418.
40. 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. e-Pub 7/23/2014. PMID: 25056119.

Invited Articles

1. Tsai KY. Assessing the treatment of nonmelanoma skin cancers. Arch Dermatol 147(5):605-6, 5/2011. PMID: 21576581.
2. Tsai KY. Introduction. Precision Medicine. Semin Cutan Med Surg 33(2):59, 6/2014. PMID: 25085662.

Abstracts

1. Adelmann CH, Pence LJ, Warthaka M, Kaoud TS, Dalby KN, Tsai KY. Personalizing MAPK inhibitor therapy with a real-time ERK activity assay. AACR Precision Medicine Series Drug Sensitivity and Resistance: Improving Cancer Therapy 2014, 6/2014.
2. Chitsazzadeh V, Nguyen T, Joseph A, Gunaratne P, Coarfa C, Su X, Flores ER, Tsai KY. Identification and functional analysis of key genetic drivers of cutaneous squamous cell carcinoma. Journal of Investigative Dermatology 134(S1):S34, 5/2014.
3. Du L, Adelmann CH, Ching G, Chitsazzadeh V, Ojeda SS, Vin H, Kaoud T, Ferguson SB, Dalby KN, Tsai KY. Off-target effects of BRAF inhibitors: Roles in SCC induction and the relationship to paradoxical ERK signaling. Journal of Investigative Dermatolology 134(S1):S91, 5/2014.
4. Vin H, Leung M, Ojeda S, Chitsazzadeh V, Dwyer D, Adelmann C, Ching G, Richards K, Stewart L, Ehrenreiter K, Baccarini M, Curry J, Kim K, Ciurea A, Duvic M, Prieto V, Ullrich S, Flores E, Tsai KY. BRAF inhibitors suppress apoptosis through off-target inhibition of JNK signaling. Pigment Cell & Melanoma Research 26(5):895, 11/2012.
5. Tsai KY, Vin H, Leung M, Chitsazzadeh V, Ojeda S, Dwyer D, Richards K, Stewart L, Curry J, Kim KB, Ciurea A, Duvic M, Prieto V, Ullrich S, Flores E. BRAF inhibitors suppress apoptosis through off-target inhibition of JNK signaling. J Clin Oncol 30(suppl; abstr 8537), 6/2012.
6. Vin H, Leung M, Ojeda S, Chitsazzadeh V, Dwyer D, Adelmann C, Ching G, Richards K, Stewart L, Ehrenreiter K, Baccarini M, Curry J, Kim K, Ciurea A, Duvic M, Prieto V, Ullrich S, Flores E, Tsai KY. BRAF inhibitors suppress apoptosis through off-target inhibition of JNK signaling. Journal of Investigative Dermatology 132(S1):S86, 6/2012.
7. Dwyer DW, Leung ML, Thompson, TB, Tsai KY. Identification of mediators of immune evasion in a modular mouse model of squamous cell carcinoma. Journal of Investigative Dermatology 131(S1):S23, 4/2011.
8. Carnevale NT, Tsai KY, Hines ML. The Electrotonic Workbench. Society for Neuroscience Abstracts 22:1741, 1996.
9. Carnevale NT, Tsai KY, Brown TH. Prediction of Hebbian learning in cells with biologically realistic electrotonic architecture. Society for Neuroscience Abstracts 21:604, 1995.
10. Carnevale NT, Tsai KY, Gonzales R, Claiborne BJ, Brown TH. Biophysical accessibility of mossy fiber synapses in rat hippocampus. Society for Neuroscience Abstracts 20:715, 1994.
11. Tsai KY, Carnevale NT, Claiborne BJ, Brown TH. Morphoelectrotonic transforms in three classes of rat hippocampal neurons. Society for Neuroscience Abstracts 19:1522, 1993.

Book Chapters

1. Tsai KY, Hoang MP. Collision tumor of malignant melanoma and monocytic sarcoma. In: Cases in Dermatopathology - Pitfalls in Dermatopathology. Ed(s) Hoang MP, Duncan LM, Mihm Jr. MC, Murphy GM, Tahan SR. Knowledge Books & Software: Brisbane, QLD, Australia, 119-128, 2008.
2. Carnevale NT, Tsai KY, Claiborne BJ, Brown TH. Qualitative electrotonic comparison of three classes of hippocampal neurons in the rat. In: The Neurobiology of Computation. Ed(s) J Bower. Kluwer Academic Publishers: Norwell, MA, 1995.
3. Carnevale NT, Tsai KY, Claiborne BJ, Brown TH. The electrotonic transformation: a tool for relating neuronal form to function. In: Advances in Neural Information Processing Systems 7. Ed(s) G Tesauro, DS Touretzky, TK Leen. MIT Press: Cambridge, MA, 69-76, 1995.
4. Tsai KY. Lymphatic Tumours. In: Rook's Textbook of Dermatology, 9. Ed(s) T Bleiker, H Tsao. Submitted.

Letters to the Editor

1. Tsai KY. A potential pathogenic role for aberrant DNA rearrangements in bridging dyscrasias of undetermined significance and lymphoma? Arch Dermatol 141(11):1468-9, 11/2005. PMID: 16301403.

Last updated: 9/7/2014