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Darwin Kwok, PhD, MS

UCSF Med Student and Part-Time Postdoc

Research Interests:

I completed a PhD in Biomedical Sciences at UCSF in 2024 under the dual mentorships of Dr. Hideho Okada and Dr. Joseph Costello. My thesis work is primarily focused on the discovery of tumor-wide public neoantigens derived from cancer-specific splicing events (neojunctions), and how aberrant splicing factor expression levels can potentially influence the recognition of neojunctions. Utilizing multi-site sampling from the same brain tumors, we captured neojunctions found tumor-wide across all biopsied sites. CD8+ T-cells engineered to express neojunction-derived neoantigen-specific T-cell receptors demonstrated robust recognition and killing of various cancer cell lines.

I am now a medical student at UCSF School of Medicine, and I lead a few exciting derivative projects from my thesis work. Firstly, I work on investigating how standard-of-care treatments, such as chemotherapy and radiation, reshapes the landscape of neojunction expression post-treatment. Secondly, I am engineering ways of augmenting specific cancer-splicing events to increase neoantigen expression levels and subsequently cytotoxicity. My thesis proved that dysregulated expression of normal splicing factors can reliably increase spliceosome recognition of specific neojunctions. Finally, I’m exploring novel approaches of developing personalized cell-based immunotherapies through peripheral blood applications.

Email: darwin.kwok@ucsf.edu

Education and Training

2012-2017 Carnegie Mellon University (Dr. Flordeliza Villanueva M.D. and Dr. John Pacella M.D., M.S.)

2017-2018 Yale University (Dr. Nikhil Joshi Ph.D.)

2018-2024 University of California, San Francisco (Dr. Hideho Okada and Dr. Joseph Costello)

2024- University of California, San Francisco, School of Medicine

Selected Awards

2024 American Medical Association (AMA) Research Challenge Semifinalist
2024 Schmidt Science Fellows Nominee
2024 AACR Scholar-in-Training Award, AACR Annual Meeting 2024
2024 Dean’s Award for Excellence in Mentoring Honorable Mention
2023 Achievement Rewards for College Scientists (ARCS) Fellowship, Michele Goss Scholar
2023 28th Annual Meeting SNO Top Poster Award
2023 38th Annual Meeting SITC Press Program Speaker
2023 Fred Hutch Cancer Center PRIMeD Selected Attendee
2023 21st Annual St. Jude National Graduate Student Symposium Awardee
2023 SITC URM Undergraduates in STEM Program Selected Presenter
2022 Gianna Rae Meadows Grant Award for Oligodendroglioma Cure
2019 NIH T32 Predoctoral Training Grant (T32GM008568)
2016 CMU College of Engineering Honors Research Program
2016 Biomedical Engineering Design Award
2016 Meeting of the Minds Symposium CIT Honors Research Finalist
2015 CMU Summer Undergraduate Research Fellowship

Featured Publications

Activating the dark genome to illuminate cancer vaccine targets.

Kwok D, Okada H, Costello J.

(2024) Nature Genetics. 56(9):1770-1771

Public tumor-wide splice-derived neoantigens drive anti-tumor T-cell responses.

Kwok D, Stevers N, Nejo T, Chen L, Etxeberria I, Jung J, Okada K, Colton Cove M, Lakshmanachetty S, Gallus M, Barpanda A, Hong C, Chan G, Wu S, Ramos E, Yamamichi A, Liu J, Watchmaker P, Ogino H, Saijo A, Du A, Grishanina N, Woo J, Diaz A, Chang S, Phillips J, Wiita A, Klebanoff C, Costello J, Okada H.

(2023) bioRxiv.

Glioblastoma evolution and heterogeneity in 3D whole-tumor space.

Mathur R, Wang Q, Schupp P, Nikolic A, Hilz S, Hong C, Grishanina N, Kwok D, Jin Q, Youngblood M, Ann Stasiak L, Hou Y, Wang J, Yamaguchi T, Stevers N, Lafontaine M, Shai A, Smirnov I, Chang S, Hervey-Jumper S, Berger M, Lupo J, Okada H, Philips J, Boutros P, Gallo M, Oldham M, Yue F, Costello J.

(2024). Cell. 187(2):446-463.

Challenges in the discovery of tumor-specific alternative splicing-derived cell-surface antigens in gliomas.

Nejo T, Wang L, Leung K, Wang A, Lakshmanachetty S, Gallus M, Kwok D, Hong C, Chen L, Carrera D, Zhang M, Stevers N, Maldonado G, Yamamichi A, Watchmaker P, Naik A, Shai A, Phillips J, Chang S, Wiita A, Wells J, Costello J, Diaz A, Okada H.

(2024) Scientific Reports. 14(1):6362.

Immunotherapy approaches in IDH-mutant low-grade glioma.

Gallus M, Kwok D, Lakshmanachetty S, Yamamichi A, Okada H.

(2023) Cancers 22;15(14):3726.

PD-1 maintains CD8 T cell tolerance towards cutaneous neoantigens.

Damo M, Hornick N, Venkat A, William I, Clulo K, Cui C, Venkatesan S, He J, Loza J, Kwok D, Tal A, Buck J, Singh J, Damsky W, Leventhal J, Krishnaswamy S, Fagerberg E, Joshi N.

(2023) Nature. 619(7968):151-159.

T-Cell based therapies for overcoming neuroanatomical and immunosuppressive challenges within the glioma microenvironment.

Kwok D, Okada H.

Journal of Neuro-Oncology (2020).147, 281-295.