Bio

Bio


Kavita Sarin, M.D. Ph.D., is a Clinical Assistant Professor of Dermatology. She has an academic interest in Personalized Medicine, focused on the integration of genetic and clinical patient data to inform disease susceptibility, stratify prognosis, and direct treatments in dermatologic disease. She sees patients in medical dermatology at Portola Valley and directs a specialized Skin Cancer Genetics clinic.

Clinical Focus


  • Dermatology
  • Bioinformatics
  • Basal Cell Carcinoma
  • Precision Dermatology
  • Skin Cancers
  • Genetic Skin Disease

Academic Appointments


Administrative Appointments


  • Clinical Instructor in Dermatology, Stanford University Medical Center (2012 - 2013)
  • Clinical Assistant Professor in Dermatology, Stanford University Medical Center (2013 - Present)

Honors & Awards


  • Medical Dermatology Career Development Award, Dermatology Foundation (2014-2017)
  • F32 NRSA Ruth L. Kirschstein National Research Service Award, National Institutes of Health (2013-2014)
  • Translational Research and Medicine Award, Stanford University (2013-2014)
  • Scholar Travel Award, American Association of Cancer Research (2006)
  • Medical Scientist Training Program Scholarship, National Institutes of Health (2000-2008)
  • 1st Place Award for Human-Computer Interaction (Senior Thesis Project), Stanford University (2000)
  • President's Scholar, Stanford University (1996-2000)
  • Unsung Hero Award, NBC (1996)

Boards, Advisory Committees, Professional Organizations


  • Fellow, American Academy of Dermatology (2009 - Present)
  • Member, Society of Investigative Dermatology (2014 - Present)
  • Member, Dermatology Foundation (2014 - Present)

Professional Education


  • Board Certification: Dermatology, American Board of Dermatology (2012)
  • Internship:Santa Clara Valley Medical Center (2009) CA
  • Residency:Stanford University - Dept of Dermatology (2012) CA
  • Medical Education:Stanford University Medical Center (2008) CA
  • PhD, Stanford University- Dept of Genetics, CA (2006)
  • BS, Stanford University- Computer Science, CA (2000)

Research & Scholarship

Current Research and Scholarly Interests


My research encompasses two main areas: 1) Using next-generation RNA, whole genome, and exome sequencing, we are investigating the genetic alterations involved in skin cancer progression, response to therapy, and other clinical outcomes and 2) We are developing and implementing genome-wide genetic risk prediction assessments for skin cancer into clinical use and studying the impact of this information on patient care.

Clinical Trials


  • Analysis of Cutaneous and Hematologic Disorders by High-Throughput Nucleic Acid Sequencing Not Recruiting

    The goal of this study is to identify genetic changes associated with the initiation, progression, and treatment response of response of cutaneous and hematologic disorders using recently developed high-throughput sequencing technologies. The improved understanding of the genetic changes associated with cutaneous and hematologic disorders may lead to improved diagnostic, prognostic and therapeutic options for these disorders.

    Stanford is currently not accepting patients for this trial. For more information, please contact Alexander Ungewickell, 650-723-6661.

    View full details

Projects


  • Genetic alterations in vismodegib resistant basal cell carcinomas, Stanford University (July 2014 - June 2017)

    The goal of this project is to identify genetic alterations that confer resistance to Smoothened inhibitor therapy in basal cell carcinoma.

    Location

    Stanford University

  • Development and implementation of a Genetic Risk Score for skin cancer prediction, Stanford University (9/1/2013 - 12/2014)

    The study aims to develop, implement and assess the impact of a genetic risk score to predict skin cancer risk based on genotypic data with the goal of understanding the barriers and benefits of implementing genetic risk analysis into clinical care

    Location

    Stanford University

Teaching

2016-17 Courses


Publications

All Publications


  • Identification of Alpha-Adrenergic Agonists as Potential Therapeutic Agents for Dermatomyositis through Drug-Repurposing Using Public Expression Datasets. journal of investigative dermatology Cho, H. G., Fiorentino, D., Lewis, M., Sirota, M., Sarin, K. Y. 2016; 136 (7): 1517-1520

    View details for DOI 10.1016/j.jid.2016.03.001

    View details for PubMedID 26975725

  • Effects of Combined Treatment With Arsenic Trioxide and Itraconazole in Patients With Refractory Metastatic Basal Cell Carcinoma. JAMA dermatology Ally, M. S., Ransohoff, K., Sarin, K., Atwood, S. X., Rezaee, M., Bailey-Healy, I., Kim, J., Beachy, P. A., Chang, A. L., Oro, A., Tang, J. Y., Colevas, A. D. 2016; 152 (4): 452-456

    Abstract

    Tumor resistance is an emerging problem for Smoothened (SMO) inhibitor-treated metastatic basal cell carcinoma (BCC). Arsenic trioxide and itraconazole antagonize the hedgehog (HH) pathway at sites distinct from those treated by SMO inhibitors.To determine whether administration of intravenous arsenic trioxide and oral itraconazole in patients with metastatic BCC is associated with a reduction in GLI1 messenger RNA expression in tumor and/or normal skin biopsy samples.Five men with metastatic BCC who experienced relapse after SMO inhibitor treatment underwent intravenous arsenic trioxide treatment for 5 days, every 28 days, and oral itraconazole treatment on days 6 to 28. Data were collected from April 10 to November 14, 2013. Follow-up was completed on October 3, 2015, and data were analyzed from June 5 to October 6, 2015.The primary outcome was the change in messenger RNA levels of the GLI family zinc finger 1 (GLI1) gene (HH-pathway target gene) in biopsy specimens of normal skin or BCC before and after treatment. Secondary objectives were evaluation of tumor response and tolerability.Of the 5 patients (mean [SD] age, 52 [9] years; age range, 43-62 years), 3 completed 3 cycles of treatment and 2 discontinued treatment early owing to disease progression or adverse events. Adverse effects included grade 2 transaminitis and grade 4 leukopenia with a grade 3 infection. Overall, arsenic trioxide and itraconazole reduced GLI1 messenger RNA levels by 75% from baseline (P < .001). The best overall response after 3 treatment cycles was stable disease in 3 patients.Targeting the HH pathway with sequential arsenic trioxide and itraconazole treatment is a feasible treatment for metastatic BCC. Although some patients experienced stable disease for 3 months, none had tumor shrinkage, which may be owing to transient GLI1 suppression with sequential dosing. Continuous dosing may be required to fully inhibit the HH pathway and achieve clinical response.

    View details for DOI 10.1001/jamadermatol.2015.5473

    View details for PubMedID 26765315

  • An Investigator-Initiated Open-Label Trial of Sonidegib in Advanced Basal Cell Carcinoma Patients Resistant to Vismodegib CLINICAL CANCER RESEARCH Danial, C., Sarin, K. Y., Oro, A. E., Chang, A. L. 2016; 22 (6): 1325-1329

    Abstract

    To assess the tumor response to the smoothened (SMO) inhibitor, sonidegib (LDE225), in patients with an advanced basal cell carcinoma (BCC) resistant to treatment with vismodegib (GDC0449).Nine patients with an advanced BCC that was previously resistant to treatment with vismodegib were given sonidegib in this investigational, open-label study. Tumor response was determined using the response evaluation criteria in solid tumors. SMO mutations were identified using biopsy samples from the target BCC location.The median duration of treatment with sonidegib was 6 weeks (range, 3-58 weeks). Five patients experienced progressive disease with sonidegib. Three patients experienced stable disease and discontinued sonidegib either due to adverse events (n = 1) or due to election for surgery (n = 2). The response of one patient was not evaluable. SMO mutations with in vitro data suggesting resistance to Hh pathway inhibition were identified in 5 patients, and none of these patients experienced responses while on sonidegib.Patients with advanced BCCs that were previously resistant to treatment with vismodegib similarly demonstrated treatment resistance with sonidegib. Patients who have developed treatment resistance to an SMO inhibitor may continue to experience tumor progression in response to other SMO inhibitors. Clin Cancer Res; 22(6); 1325-9. ©2015 AACR.

    View details for DOI 10.1158/1078-0432.CCR-15-1588

    View details for Web of Science ID 000373358900006

    View details for PubMedID 26546616

  • Familial skin cancer syndromes Increased risk of nonmelanotic skin cancers and extracutaneous tumors JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY Jaju, P. D., Ransohoff, K. J., Tang, J. Y., Sarin, K. Y. 2016; 74 (3): 437-451

    Abstract

    Nonmelanoma skin cancers (NMSCs) represent the most common malignancies worldwide, with reported incidence rising each year. Both cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), as well as other NMSCs, represent complex diseases with a combination of environmental and genetic risk factors. In general, hereditary cancer syndromes that increase the risk of NMSC fall under several broad categories: those associated with immunodeficiencies, those that affect skin pigmentation, and those that perturb key molecular pathways involved in the pathogenesis of NMSCs. Many of the syndromes are also associated with extracutaneous manifestations, including internal malignancies; therefore, most require a multidisciplinary management approach with a medical geneticist. Finally, dermatologists play a critical role in the diagnosis and management of these conditions, because cutaneous findings are often the presenting manifestations of disease.

    View details for DOI 10.1016/j.jaad.2015.08.073

    View details for Web of Science ID 000370372300008

    View details for PubMedID 26892653

  • Familial skin cancer syndromes Increased melanoma risk JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY Ransohoff, K. J., Jaju, P. D., Tang, J. Y., Carbone, M., Leachman, S., Sarin, K. Y. 2016; 74 (3): 423-434

    Abstract

    Phenotypic traits, such as red hair and freckling, increase melanoma risk by 2- to 3-fold. In addition, approximately 10% of melanomas are caused by inherited germline mutations that increase melanoma risk from 4- to >1000-fold. This review highlights the key genes responsible for inherited melanoma, with an emphasis on when a patient should undergo genetic testing. Many genetic syndromes associated with increased melanoma risk are also associated with an increased risk of other cancers. Identification of these high-risk patients is essential for preventive behavior reinforcement, genetic counseling, and ensuring other required cancer screenings.

    View details for DOI 10.1016/j.jaad.2015.09.070

    View details for Web of Science ID 000370372300007

    View details for PubMedID 26892652

  • A survey of direct-to-consumer teledermatology services available to US patients: Explosive growth, opportunities, and controversy Journal of telemedicine and telecare Fogel, A. L., Sarin, K. Y. 2016
  • Genome-wide association study identifies novel susceptibility loci for cutaneous squamous cell carcinoma. Nature communications Chahal, H. S., Lin, Y., Ransohoff, K. J., Hinds, D. A., Wu, W., Dai, H., Qureshi, A. A., Li, W., Kraft, P., Tang, J. Y., Han, J., Sarin, K. Y. 2016; 7: 12048-?

    Abstract

    Cutaneous squamous cell carcinoma represents the second most common cutaneous malignancy, affecting 7-11% of Caucasians in the United States. The genetic determinants of susceptibility to cutaneous squamous cell carcinoma remain largely unknown. Here we report the results of a two-stage genome-wide association study of cutaneous squamous cell carcinoma, totalling 7,404 cases and 292,076 controls. Eleven loci reached genome-wide significance (P<5 × 10(-8)) including seven previously confirmed pigmentation-related loci: MC1R, ASIP, TYR, SLC45A2, OCA2, IRF4 and BNC2. We identify an additional four susceptibility loci: 11q23.3 CADM1, a metastasis suppressor gene involved in modifying tumour interaction with cell-mediated immunity; 2p22.3; 7p21.1 AHR, the dioxin receptor involved in anti-apoptotic pathways and melanoma progression; and 9q34.3 SEC16A, a putative oncogene with roles in secretion and cellular proliferation. These susceptibility loci provide deeper insight into the pathogenesis of squamous cell carcinoma.

    View details for DOI 10.1038/ncomms12048

    View details for PubMedID 27424798

  • Genome-wide association study identifies 14 novel risk alleles associated with basal cell carcinoma. Nature communications Chahal, H. S., Wu, W., Ransohoff, K. J., Yang, L., Hedlin, H., Desai, M., Lin, Y., Dai, H., Qureshi, A. A., Li, W., Kraft, P., Hinds, D. A., Tang, J. Y., Han, J., Sarin, K. Y. 2016; 7: 12510-?

    Abstract

    Basal cell carcinoma (BCC) is the most common cancer worldwide with an annual incidence of 2.8 million cases in the United States alone. Previous studies have demonstrated an association between 21 distinct genetic loci and BCC risk. Here, we report the results of a two-stage genome-wide association study of BCC, totalling 17,187 cases and 287,054 controls. We confirm 17 previously reported loci and identify 14 new susceptibility loci reaching genome-wide significance (P<5 × 10(-8), logistic regression). These newly associated SNPs lie within predicted keratinocyte regulatory elements and in expression quantitative trait loci; furthermore, we identify candidate genes and non-coding RNAs involved in telomere maintenance, immune regulation and tumour progression, providing deeper insight into the pathogenesis of BCC.

    View details for DOI 10.1038/ncomms12510

    View details for PubMedID 27539887

  • Effects of combined treatment with arsenic trioxide and itraconazole in patients with refractory metastatic basal cell carcinoma JAMA Dermatology Sarin, K. Y., Ally, M. S., Ransohoff, K. J., Atwood, S. X., Rezaee, M. 2016
  • Familial skin cancer syndromes: Increased melanoma risk Journal of The American Academy of Dermatology Jaju, P. D., Ransohoff, K. J., Tang, J. Y., Sarin, K. Y. 2016; 74 (3): 423-434
  • Familial skin cancer syndromes: Increased risk of nonmelanotic skin cancers and extracutaneous tumors Journal of The American Academy of Dermatology Sarin, K. Y., Tang, J. Y., Ransohoff, K. J., Jaju, P. D. 2016; 74 (3): 437-451
  • Mutations in the Kinetochore Gene KNSTRN in Basal Cell Carcinoma. journal of investigative dermatology Jaju, P. D., Nguyen, C. B., Mah, A. M., Atwood, S. X., Li, J., Zia, A., Chang, A. L., Oro, A. E., Tang, J. Y., Lee, C. S., Sarin, K. Y. 2015; 135 (12): 3197-3200

    View details for DOI 10.1038/jid.2015.339

    View details for PubMedID 26348826

  • Squamous Change in Basal-Cell Carcinoma with Drug Resistance NEW ENGLAND JOURNAL OF MEDICINE Ransohoff, K. J., Tang, J. Y., Sarin, K. Y. 2015; 373 (11): 1079-1082
  • Smoothened Inhibitors in Sonic Hedgehog Subgroup Medulloblastoma. Journal of clinical oncology Ransohoff, K. J., Sarin, K. Y., Tang, J. Y. 2015; 33 (24): 2692-2694

    View details for DOI 10.1200/JCO.2015.62.2225

    View details for PubMedID 26195713

  • Rolling the Genetic Dice: Neutral and Deleterious Smoothened Mutations in Drug-Resistant Basal Cell Carcinoma. journal of investigative dermatology Atwood, S. X., Sarin, K. Y., Li, J. R., Yao, C. Y., Urman, N. M., Chang, A. L., Tang, J. Y., Oro, A. E. 2015; 135 (8): 2138-2141

    View details for DOI 10.1038/jid.2015.115

    View details for PubMedID 25801792

  • A subdermal source: contact dermatitis. American journal of medicine Fogel, A. L., Longmire, M., Rieger, K. E., Sarin, K. Y. 2015; 128 (6): 578-581

    View details for DOI 10.1016/j.amjmed.2015.02.005

    View details for PubMedID 25747191

  • Genomic Analysis of Smoothened Inhibitor Resistance in Basal Cell Carcinoma CANCER CELL Sharpe, H. J., Pau, G., Dijkgraaf, G. J., Basset-Seguin, N., Modrusan, Z., Januario, T., Tsui, V., Durham, A. B., Dlugosz, A. A., Haverty, P. M., Bourgon, R., Tang, J. Y., Sarin, K. Y., Dirix, L., Fisher, D. C., Rudin, C. M., Sofen, H., Migden, M. R., Yauch, R. L., de Sauvage, F. J. 2015; 27 (3): 327-341

    Abstract

    Smoothened (SMO) inhibitors are under clinical investigation for the treatment of several cancers. Vismodegib is approved for the treatment of locally advanced and metastatic basal cell carcinoma (BCC). Most BCC patients experience significant clinical benefit on vismodegib, but some develop resistance. Genomic analysis of tumor biopsies revealed that vismodegib resistance is associated with Hedgehog (Hh) pathway reactivation, predominantly through mutation of the drug target SMO and to a lesser extent through concurrent copy number changes in SUFU and GLI2. SMO mutations either directly impaired drug binding or activated SMO to varying levels. Furthermore, we found evidence for intra-tumor heterogeneity, suggesting that a combination of therapies targeting components at multiple levels of the Hh pathway is required to overcome resistance.

    View details for DOI 10.1016/j.ccell.2015.02.001

    View details for Web of Science ID 000350977200006

  • Smoothened Variants Explain the Majority of Drug Resistance in Basal Cell Carcinoma CANCER CELL Atwood, S. X., Sarin, K. Y., Whitson, R. J., Li, J. R., Kim, G., Rezaee, M., Ally, M. S., Kim, J., Yao, C., Chang, A. L., Oro, A. E., Tang, J. Y. 2015; 27 (3): 342-353

    Abstract

    Advanced basal cell carcinomas (BCCs) frequently acquire resistance to Smoothened (SMO) inhibitors through unknown mechanisms. Here we identify SMO mutations in 50% (22 of 44) of resistant BCCs and show that these mutations maintain Hedgehog signaling in the presence of SMO inhibitors. Alterations include four ligand binding pocket mutations defining sites of inhibitor binding and four variants conferring constitutive activity and inhibitor resistance, illuminating pivotal residues that ensure receptor autoinhibition. In the presence of a SMO inhibitor, tumor cells containing either class of SMO mutants effectively outcompete cells containing the wild-type SMO. Finally, we show that both classes of SMO variants respond to aPKC-ι/λ or GLI2 inhibitors that operate downstream of SMO, setting the stage for the clinical use of GLI antagonists.

    View details for DOI 10.1016/j.ccell.2015.02.002

    View details for Web of Science ID 000350977200007

  • An investigator-initiated open label trial of sonidegib in advanced basal cell carcinoma patients resistant to vismodegib Clinical cancer research: an official journal of the American Association for Cancer Research Sarin, K. Y., Oro, A. E., Chang, A. L., Danial, C. 2015
  • The digital age of melanoma management: detection and diagnostics Future Medicine Fogel, A. L., Sarin, K. Y. 2015; 2 (4): 383-391

    View details for DOI 10.2217/mmt.15.31

  • Dermatologic applications of direct-to-consumer genomic analysis. Journal of the American Academy of Dermatology Fogel, A. L., Azizi, N., Tang, J., Sarin, K. Y. 2014; 71 (5): 993-995

    View details for DOI 10.1016/j.jaad.2014.04.066

    View details for PubMedID 25437956

  • Activating HRAS Mutation in Nevus Spilus. journal of investigative dermatology Sarin, K. Y., McNiff, J. M., Kwok, S., Kim, J., Khavari, P. A. 2014; 134 (6): 1766-1768

    View details for DOI 10.1038/jid.2014.6

    View details for PubMedID 24390138

  • Dermatomyositis associated with capecitabine in the setting of malignancy JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY Chen, F. W., Zhou, X., Egbert, B. M., Swetter, S. M., Sarin, K. Y. 2014; 70 (2): E47-E48

    View details for DOI 10.1016/j.jaad.2013.10.025

    View details for Web of Science ID 000329851500013

    View details for PubMedID 24438983

  • Activating HRAS mutation in agminated Spitz nevi arising in a nevus spilus. JAMA dermatology Sarin, K. Y., Sun, B. K., Bangs, C. D., Cherry, A., Swetter, S. M., Kim, J., Khavari, P. A. 2013; 149 (9): 1077-1081

    Abstract

    IMPORTANCE Spitz nevi are benign melanocytic proliferations that can sometimes be clinically and histopathologically difficult to distinguish from melanoma. Agminated Spitz nevi have been reported to arise spontaneously, in association with an underlying nevus spilus, or after radiation or chemotherapy. However, to our knowledge, the genetic mechanism for this eruption has not been described. OBSERVATIONS We report a case of agminated Spitz nevi arising in a nevus spilus and use exome sequencing to identify a clonal activating point mutation in HRAS (GenBank 3265) (c.37G→C) in the Spitz nevi and underlying nevus spilus. We also identify a secondary copy number increase involving HRAS on chromosome 11p, which occurs during the development of the Spitz nevi. CONCLUSIONS AND RELEVANCE Our results reveal an activating HRAS mutation in a nevus spilus that predisposes to the formation of Spitz nevi. In addition, we demonstrate a copy number increase in HRAS as a "second hit" during the formation of agminated Spitz nevi, which suggests that both multiple Spitz nevi and solitary Spitz nevi may arise through similar molecular pathways. In addition, we describe a unique investigative approach for the discovery of genetic alterations in Spitz nevi.

    View details for DOI 10.1001/jamadermatol.2013.4745

    View details for PubMedID 23884457

  • Mosaic Activating RAS Mutations in Nevus Sebaceus and Nevus Sebaceus Syndrome JOURNAL OF INVESTIGATIVE DERMATOLOGY Sun, B. K., Saggini, A., Sarin, K. Y., Kim, J., Benjamin, L., LeBoit, P. E., Khavari, P. A. 2013; 133 (3): 824-827

    View details for DOI 10.1038/jid.2012.377

    View details for Web of Science ID 000315008500032

    View details for PubMedID 23096709

  • Molecular Profiling to Diagnose a Case of Atypical Dermatomyocitis Journal of Investigative Dermatology Sarin, K., Chung, L., Kim, J., Higgs, B., Jallal, B., Yao, Y., Fiorentino, D. 2013; 133 (12): 2796-2799
  • Treatment of Recalcitrant Eosinophilic Cellulitis With Adalimumab ARCHIVES OF DERMATOLOGY Sarin, K. Y., Fiorentino, D. 2012; 148 (9): 990-992

    View details for Web of Science ID 000308883500002

    View details for PubMedID 22986848

  • Reversible cell-cycle entry in adult kidney podocytes through regulated control of telomerase and Wnt signaling. Nature medicine Shkreli, M., Sarin, K. Y., Pech, M. F., Papeta, N., Chang, W., Brockman, S. A., Cheung, P., Lee, E., Kuhnert, F., Olson, J. L., Kuo, C. J., Gharavi, A. G., D'Agati, V. D., Artandi, S. E. 2012; 18 (1): 111-119

    Abstract

    Mechanisms of epithelial cell renewal remain poorly understood in the mammalian kidney, particularly in the glomerulus, a site of cellular damage in chronic kidney disease. Within the glomerulus, podocytes--differentiated epithelial cells crucial for filtration--are thought to lack substantial capacity for regeneration. Here we show that podocytes rapidly lose differentiation markers and enter the cell cycle in adult mice in which the telomerase protein component TERT is conditionally expressed. Transgenic TERT expression in mice induces marked upregulation of Wnt signaling and disrupts glomerular structure, resulting in a collapsing glomerulopathy resembling those in human disease, including HIV-associated nephropathy (HIVAN). Human and mouse HIVAN kidneys show increased expression of TERT and activation of Wnt signaling, indicating that these are general features of collapsing glomerulopathies. Silencing transgenic TERT expression or inhibiting Wnt signaling through systemic expression of the Wnt inhibitor Dkk1 in either TERT transgenic mice or in a mouse model of HIVAN results in marked normalization of podocytes, including rapid cell-cycle exit, re-expression of differentiation markers and improved filtration barrier function. These data reveal an unexpected capacity of podocytes to reversibly enter the cell cycle, suggest that podocyte renewal may contribute to glomerular homeostasis and implicate the telomerase and Wnt-β-catenin pathways in podocyte proliferation and disease.

    View details for DOI 10.1038/nm.2550

    View details for PubMedID 22138751

  • TERT promotes epithelial proliferation through transcriptional control of a Myc- and Wnt-related developmental program PLOS GENETICS Choi, J., Southworth, L. K., Sarin, K. Y., Venteicher, A. S., Ma, W., Chang, W., Cheung, P., Jun, S., Artandi, M. K., Shah, N., Kim, S. K., Artandi, S. E. 2008; 4 (1)

    Abstract

    Telomerase serves a critical role in stem cell function and tissue homeostasis. This role depends on its ability to synthesize telomere repeats in a manner dependent on the reverse transcriptase (RT) function of its protein component telomerase RT (TERT), as well as on a novel pathway whose mechanism is poorly understood. Here, we use a TERT mutant lacking RT function (TERT(ci)) to study the mechanism of TERT action in mammalian skin, an ideal tissue for studying progenitor cell biology. We show that TERT(ci) retains the full activities of wild-type TERT in enhancing keratinocyte proliferation in skin and in activating resting hair follicle stem cells, which triggers initiation of a new hair follicle growth phase and promotes hair synthesis. To understand the nature of this RT-independent function for TERT, we studied the genome-wide transcriptional response to acute changes in TERT levels in mouse skin. We find that TERT facilitates activation of progenitor cells in the skin and hair follicle by triggering a rapid change in gene expression that significantly overlaps the program controlling natural hair follicle cycling in wild-type mice. Statistical comparisons to other microarray gene sets using pattern-matching algorithms revealed that the TERT transcriptional response strongly resembles those mediated by Myc and Wnt, two proteins intimately associated with stem cell function and cancer. These data show that TERT controls tissue progenitor cells via transcriptional regulation of a developmental program converging on the Myc and Wnt pathways.

    View details for DOI 10.1371/journal.pgen.0040010

    View details for Web of Science ID 000255378700011

    View details for PubMedID 18208333

  • Aging, graying and loss of melanocyte stem cells STEM CELL REVIEWS Sarin, K. Y., Artandi, S. E. 2007; 3 (3): 212-217

    Abstract

    Hair graying is one of the prototypical signs of human aging. Maintenance of hair pigmentation is dependent on the presence and functionality of melanocytes, neural crest derived cells which synthesize pigment for growing hair. The melanocytes, themselves, are maintained by a small number of stem cells which reside in the bulge region of the hair follicle. The recent characterization of the melanocyte lineage during aging has significantly accelerated our understanding of how age-related changes in the melanocyte stem cell compartment contribute to hair graying. This review will discuss our current understanding of hair graying, drawing on evidence from human and mouse studies, and consider the contribution of melanocyte stem cells to this process. Furthermore, using the melanocyte lineage as an example, it will discuss common theories of tissue and stem cell aging.

    View details for DOI 10.1007/s12015-007-0028-0

    View details for Web of Science ID 000249929800004

    View details for PubMedID 17917134

  • Conditional telomerase induction causes proliferation of hair follicle stem cells NATURE Sarin, K. Y., Cheung, P., Gilison, D., Lee, E., Tennen, R. I., Wang, E., Artandi, M. K., Oro, A. E., Artandi, S. E. 2005; 436 (7053): 1048-1052

    Abstract

    TERT, the protein component of telomerase, serves to maintain telomere function through the de novo addition of telomere repeats to chromosome ends, and is reactivated in 90% of human cancers. In normal tissues, TERT is expressed in stem cells and in progenitor cells, but its role in these compartments is not fully understood. Here we show that conditional transgenic induction of TERT in mouse skin epithelium causes a rapid transition from telogen (the resting phase of the hair follicle cycle) to anagen (the active phase), thereby facilitating robust hair growth. TERT overexpression promotes this developmental transition by causing proliferation of quiescent, multipotent stem cells in the hair follicle bulge region. This new function for TERT does not require the telomerase RNA component, which encodes the template for telomere addition, and therefore operates through a mechanism independent of its activity in synthesizing telomere repeats. These data indicate that, in addition to its established role in extending telomeres, TERT can promote proliferation of resting stem cells through a non-canonical pathway.

    View details for DOI 10.1038/nature03836

    View details for Web of Science ID 000231263900057

    View details for PubMedID 16107853