Iwei Yeh, MD, PhD

New Academic
M_Dermatology
+1 415 353-7989

The unifying theme of my research is to understand the genetic mechanisms involved in the development and progression of melanocytic skin tumors and harness our understanding to improve melanoma treatment. I am well positioned to accomplish this goal since I am an expert dermatopathologist and a scientist with expertise in cancer genetics and bioinformatics. My efforts have been focused on identifying oncogenic drivers in melanocytic tumors, with the goal to identify and move new knowledge from the laboratory directly to patient care. By combining the histopathologic classification with a better understanding of the biology of melanocytic tumors gained in the laboratory I seek to make a significant impact on patient care.

My work has contributed to our understanding of the initiating oncogenic events in melanocytic tumors. In 2013 I was the lead author of an article in the Journal of the National Cancer Institute definitively showing that BRAF mutations are both clonal and heterozygous in melanocytic nevi, thereby establishing that they are initiating events. Subsequently, I worked to identify an array of kinase gene fusions in Spitz tumors, with lead author publications in Nature Communications and the Journal of Pathology describing the discovery of MET and NTRK3 gene fusions as initiating events in Spitz tumors.

In a 2015 New England Journal of Medicine paper, I was a member of the team that identified multiple pathways of genetic progression in melanocytic tumors and showed that the diagnostically controversial entity "dysplastic nevus" has more oncogenic drivers than benign nevi and fewer than melanoma. This work demonstrated for the very first time that the step-wise progression model of cancer also applies to melanocytic tumors and forms the groundwork for future studies further delineating the diverse pathways of melanoma progression and potential targets for therapeutic intervention. In 2017 I was the lead author of an article in Nature Communications demonstrating that activating mutations of beta-catenin lead to progression of conventional nevus to deep penetrating nevus.

A particular area of interest is the genetics of acral and mucosal melanomas. These melanomas arise in sun-protected sites and typically do not harbor a large number of ultraviolet light induced mutations but instead have highly rearranged genomes with many amplifications and deletions. Our group has developed new methodologies for genomically profiling small archival tissue samples and used this technique to identify SPRED1 as a tumor suppressor in mucosal melanoma. In a publication in Science, we demonstrated that loss of SPRED1 cooperates with KIT mutation and that dual inhibition of KIT and MEK is synergistic against KIT mutant melanomas with SPRED1 loss. These findings are currently being translated to the clinic through an investigator-initated clinical trial in collaboration with UCSF melanoma oncology.

Publications

Evaluation and Surgical Management of Pediatric Cutaneous Melanoma and Atypical Spitz and Non-Spitz Melanocytic Tumors (Melanocytomas): A Report From Children's Oncology Group.

Journal of clinical oncology : official journal of the American Society of Clinical Oncology

Sargen MR, Barnhill RL, Elder DE, Swetter SM, Prieto VG, Ko JS, Bahrami A, Gerami P, Karunamurthy A, Pappo AS, Schuchter LM, LeBoit PE, Yeh I, Kirkwood JM, Jen M, Dunkel IJ, Durham MM, Christison-Lagay ER, Austin MT, Aldrink JH, Mehrhoff C, Hawryluk EB, Chu EY, Busam KJ, Sondak V, Messina J, Puig S, Colebatch AJ, Coughlin CC, Berrebi KG, Laetsch TW, Mitchell SG, Seynnaeve B

The genetic evolution of acral melanoma.

Nature communications

Wang M, Fukushima S, Sheen YS, Ramelyte E, Cruz-Pacheco N, Shi C, Liu S, Banik I, Aquino JD, Sangueza Acosta M, Levesque M, Dummer R, Liau JY, Chu CY, Shain AH, Yeh I, Bastian BC

Molecular effects of indoor tanning.

bioRxiv : the preprint server for biology

Gerami P, Tandukar B, Deivendran D, Olivares S, Chen L, Tang J, Tan T, Sharma H, Bandari AK, Cruz-Pacheco N, Chang D, Marty A, Olshen A, Murad NF, Song J, Lee J, Yeh I, Hunter Shain A

The Impact of Next-generation Sequencing on Interobserver Agreement and Diagnostic Accuracy of Desmoplastic Melanocytic Neoplasms.

The American journal of surgical pathology

Chen A, Sharma N, Patel P, Olivares S, Bahrami A, Barnhill RL, Blokx WAM, Bosenberg M, Busam KJ, de La Fouchardière A, Duncan LM, Elder DE, Ko JS, Landman G, Lazar AJ, Lezcano C, Lowe L, Maher N, Massi D, Messina J, Mihic-Probst D, Parker DC, Redpath M, Scolyer RA, Shea CR, Spatz A, Tron V, Xu X, Yeh I, Jung Yun S, Zembowicz A, Gerami P

The genetic evolution of acral melanoma.

bioRxiv : the preprint server for biology

Wang M, Fukushima S, Sheen YS, Ramelyte E, Pacheco NC, Shi C, Liu S, Banik I, Aquino JD, Acosta MS, Levesque M, Dummer R, Liau JY, Chu CY, Shain AH, Yeh I, Bastian BC

Melanoma models for the next generation of therapies.

Cancer cell

Patton EE, Mueller KL, Adams DJ, Anandasabapathy N, Aplin AE, Bertolotto C, Bosenberg M, Ceol CJ, Burd CE, Chi P, Herlyn M, Holmen SL, Karreth FA, Kaufman CK, Khan S, Kobold S, Leucci E, Levy C, Lombard DB, Lund AW, Marie KL, Marine JC, Marais R, McMahon M, Robles-Espinoza CD, Ronai ZA, Samuels Y, Soengas MS, Villanueva J, Weeraratna AT, White RM, Yeh I, Zhu J, Zon LI, Hurlbert MS, Merlino G

Co-occurring Alterations in the RAS-MAPK Pathway Limit Response to MET Inhibitor Treatment in MET Exon 14 Skipping Mutation-Positive Lung Cancer.

Clinical cancer research : an official journal of the American Association for Cancer Research

Rotow JK, Gui P, Wu W, Raymond VM, Lanman RB, Kaye FJ, Peled N, Fece de la Cruz F, Nadres B, Corcoran RB, Yeh I, Bastian BC, Starostik P, Newsom K, Olivas VR, Wolff AM, Fraser JS, Collisson EA, McCoach CE, Camidge DR, Pacheco J, Bazhenova L, Li T, Bivona TG, Blakely CM

Whole-genome landscape of mucosal melanoma reveals diverse drivers and therapeutic targets.

Nature communications

Newell F, Kong Y, Wilmott JS, Johansson PA, Ferguson PM, Cui C, Li Z, Kazakoff SH, Burke H, Dodds TJ, Patch AM, Nones K, Tembe V, Shang P, van der Weyden L, Wong K, Holmes O, Lo S, Leonard C, Wood S, Xu Q, Rawson RV, Mukhopadhyay P, Dummer R, Levesque MP, Jönsson G, Wang X, Yeh I, Wu H, Joseph N, Bastian BC, Long GV, Spillane AJ, Shannon KF, Thompson JF, Saw RPM, Adams DJ, Si L, Pearson JV, Hayward NK, Waddell N, Mann GJ, Guo J, Scolyer RA

The genetic landscape of gliomas arising after therapeutic radiation.

Acta neuropathologica

López GY, Van Ziffle J, Onodera C, Grenert JP, Yeh I, Bastian BC, Clarke J, Oberheim Bush NA, Taylor J, Chang S, Butowski N, Banerjee A, Mueller S, Kline C, Torkildson J, Samuel D, Siongco A, Raffel C, Gupta N, Kunwar S, Mummaneni P, Aghi M, Theodosopoulos P, Berger M, Phillips JJ, Pekmezci M, Tihan T, Bollen AW, Perry A, Solomon DA

NTRK3 kinase fusions in Spitz tumours.

The Journal of pathology

Yeh I, Tee MK, Botton T, Shain AH, Sparatta AJ, Gagnon A, Vemula SS, Garrido MC, Nakamaru K, Isoyama T, McCalmont TH, LeBoit PE, Bastian BC

Melanoma BRAF fusions--letter.

Clinical cancer research : an official journal of the American Association for Cancer Research

Botton T, Yeh I, Bastian BC