Clara Liu

Program: Computational and Systems Biology

Current advisor: Li Ding, PhD

Undergraduate university: Cornell University, 2019

Enrollment year: 2019

Research summary
Multi-omic investigation of tumor evolution under hypoxia in treatment resistance, local spatial invasion, and distant metastasis

Clonal evolution describes the process where tumor cells accumulate a series of genetic alterations during the malignant transformation. Treatment-resistant and metastatic subclones often arise in cancer through differential oncogenic processes and unfavorable interactions with the tumor microenvironment (TME). Bulk and dissociative single-cell sequencing of multi-regional and longitudinal tumor samples have demonstrated diverse tumor clonal evolution patterns. However, recent advances in spatial-omic technologies allow for the direct observation of tumor invasion in the TME, which provides a unique angle in understanding this complex process. In my thesis, I aim to characterize temporal and spatial tumor clonal evolution and dissect it into a function of tumor-intrinsic progression and differential interactions with the TME.

Graduate publications
Liu J, Cao S, Imbach KJ, Gritsenko MA, Lih TM, Kyle JE, Yaron-Barir TM, Binder ZA, Li Y, Strunilin I, Wang YT, Tsai CF, Ma W, Chen L, Clark NM, Shinkle A, Naser Al Deen N, Caravan W, Houston A, Simin FA, Wyczalkowski MA, Wang LB, Storrs E, Chen S, Illindala R, Li YD, Jayasinghe RG, Rykunov D, Cottingham SL, Chu RK, Weitz KK, Moore RJ, Sagendorf T, Petyuk VA, Nestor M, Bramer LM, Stratton KG, Schepmoes AA, Couvillion SP, Eder J, Kim YM, Gao Y, Fillmore TL, Zhao R, Monroe ME, Southard-Smith AN, Li YE, Jui-Hsien Lu R, Johnson JL, Wiznerowicz M, Hostetter G, Newton CJ, Ketchum KA, Thangudu RR, Barnholtz-Sloan JS, Wang P, Fenyö D, An E, Thiagarajan M, Robles AI, Mani DR, Smith RD, Porta-Pardo E, Cantley LC, Iavarone A, Chen F, Mesri M, Nasrallah MP, Zhang H, Resnick AC, Chheda MG, Rodland KD, Liu T, Ding L; Philadelphia Coalition for a Cure; Clinical Proteomic Tumor Analysis Consortium. 2024 Multi-scale signaling and tumor evolution in high-grade gliomas. Cancer Cell, 42(7):1217-1238.e19. PMCID:

Terekhanova NV, Karpova A, Liang WW, Strzalkowski A, Chen S, Li Y, Southard-Smith AN, Iglesia MD, Wendl MC, Jayasinghe RG, Liu J, Song Y, Cao S, Houston A, Liu X, Wyczalkowski MA, Lu RJ, Caravan W, Shinkle A, Naser Al Deen N, Herndon JM, Mudd J, Ma C, Sarkar H, Sato K, Ibrahim OM, Mo CK, Chasnoff SE, Porta-Pardo E, Held JM, Pachynski R, Schwarz JK, Gillanders WE, Kim AH, Vij R, DiPersio JF, Puram SV, Chheda MG, Fuh KC, DeNardo DG, Fields RC, Chen F, Raphael BJ, Ding L. 2023 Epigenetic regulation during cancer transitions across 11 tumour types. Nature, 623(7986):432-41. PMCID: PMC10632147

Cui Zhou D, Jayasinghe RG, Chen S, Herndon JM, Iglesia MD, Navale P, Wendl MC, Caravan W, Sato K, Storrs E, Mo CK, Liu J, Southard-Smith AN, Wu Y, Naser Al Deen N, Baer JM, Fulton RS, Wyczalkowski MA, Liu R, Fronick CC, Fulton LA, Shinkle A, Thammavong L, Zhu H, Sun H, Wang LB, Li Y, Zuo C, McMichael JF, Davies SR, Appelbaum EL, Robbins KJ, Chasnoff SE, Yang X, Reeb AN, Oh C, Serasanambati M, Lal P, Varghese R, Mashl JR, Ponce J, Terekhanova NV, Yao L, Wang F, Chen L, Schnaubelt M, Lu RJ, Schwarz JK, Puram SV, Kim AH, Song SK, Shoghi KI, Lau KS, Ju T, Chen K, Chatterjee D, Hawkins WG, Zhang H, Achilefu S, Chheda MG, Oh ST, Gillanders WE, Chen F, DeNardo DG, Fields RC, Ding L. 2022 Spatially restricted drivers and transitional cell populations cooperate with the microenvironment in untreated and chemo-resistant pancreatic cancer. Nat Genet, 54(9):1390-1405. PMCID: PMC9470535