Cheng Wang Lab

Overview

The global burden of gynecologic malignancies remains a critical public health crisis. According to recent global cancer statistics, more than 1.4 million women are diagnosed with gynecologic cancers annually, resulting in over 680,000 deaths. These staggering mortality rates are driven, in part, by a fundamental knowledge gap: the precise molecular events underlying gynecologic cancer initiation, immune evasion, and metastasis remain incompletely understood. Research in my laboratory primarily focuses on identifying the signaling pathways and molecular drivers that contribute to physiological and pathological changes in the female reproductive tract (ovaries, fallopian tubes, uterus, and cervix). Specifically, we are investigating the role of the Hippo/YAP signaling pathway in tissue homeostasis and oncogenesis. Our overarching mission is to translate these mechanistic discoveries into novel strategies for the effective prevention, early diagnosis, and targeted treatment of lethal gynecological malignancies, ultimately saving women’s lives.

Research Projects

Defining the functional significance of the Hippo/YAP signaling pathway in the initiation and progression of high-grade serious ovarian cancer (HGSC)

Ovarian cancer remains the most lethal gynecological malignancy in Western countries. Despite rapid progress in research over the past few decades, the survival rate for epithelial ovarian cancer has not significantly improved. Our laboratory aims to uncover the molecular mechanisms by which environmental pathogens interact with intrinsic genetic and genomic alterations in the fallopian tube and ovarian tissues to drive the development of HGSC. Our previous studies identified the disrupted Hippo/YAP signaling pathway as a critical contributor to HGSC development (Endocrine-Related Cancer, 2014; Oncogene, 2015, 2016; EMBO Rep, 2019; Sci Bull, 2020; EMBO Rep, 2024; Nature Communications, 2025).

Currently, we are utilizing sophisticated transgenic animal models to investigate how sexually transmitted pathogens modulate Hippo/YAP signaling to trigger the malignant transformation of ovarian and fallopian tube epithelial cells. We expect this project to provide essential insights into HGSC etiology and offer new clues to improve current prevention and treatment strategies. This project is supported by NIH, Colleen’s Dream Foundation, Rivkin Center for Ovarian Cancer Research, the Ruggles Family Foundation, and VCRB/MGH Research Funds.

Uncovering Novel Mechanisms Underlying Cervical Carcinogenesis (CvC)

Cervical cancer (CvC) is the fourth leading cause of cancer death in women. Because over 95% of CvC patients test positive for human papillomavirus (HPV) DNA, it is widely accepted that high-risk HPV (hrHPV) causes these cases. However, accumulating evidence indicates that hrHPV alone is insufficient to induce carcinogenesis; individual genetic and genomic factors also play a critical role. Research in our laboratory has demonstrated that YAP1, the major effector of the Hippo tumor-suppressive pathway, interacts with hrHPV to drive epithelial cell transformation (EMBO Molecular Medicine, 2015, oncogene, 2022). Supported by the NIH, we generated a unique transgenic mouse model revealing that hyperactivation of YAP1 can initiate invasive CvC in the absence of hrHPV (Cell Reports, 2019), directly challenging the HPV-only dogma. Our recent mechanistic studies further show that YAP1 and LATS2 form a negative feedback loop to maintain tissue homeostasis (EMBO Reports, 2019). Disruption of this loop by HPV or intrinsic factors blocks YAP1-induced senescence, leading to malignant transformation (oncogene, 2022). Our ongoing studies focus on translating these bench-side findings into bedside diagnostic and therapeutic tools. This project is supported by NIH, the Ruggles Family Foundation, and VCRB/MGH Funds.

Innovative Strategies for Uterine Cancer Prevention and Intervention

Uterine cancer (EC) represents a profound and escalating public health crisis. In 2022, an estimated 65,950 American women were diagnosed with uterine cancer, with 13,860 deaths. While the U.S. accounts for only 4.2% of the global population, it represents a staggering 15.7% of worldwide EC incidence and 12.8% of EC-associated deaths. Furthermore, EC is one of the few malignancies exhibiting an alarming increase in both incidence and mortality, with U.S. cases surging from 40,880 in 2005 to an estimated 69,120 in 2025.

The significant decline in CvC rates demonstrates that proactive prevention is a viable strategy to reverse fatal trends. However, there are currently no routine, population-wide screening programs for EC. Leveraging our highly specialized expertise in engineering complex transgenic models of the female reproductive tract, we systematically integrate human genomic data with advanced in vivo modeling to map unexplored pathways involved in EC initiation and progression. Our goal is to develop accessible, low-toxicity prevention and intervention approaches to save women’s lives from uterine cancer, particularly highly aggressive uterine serous carcinoma (USC). This study is supported by the Ruggles Family Foundation and VCRB/MGH Funds.

Research Team

Jiyuan Liu, PhD – Postdoctoral Research Fellow

Jiyuan is a biomedical researcher with combined expertise in bench work and bioinformatics. He was trained in basic and translational biomedical research and earned his PhD in nutrition science from China Agricultural University (CAU) in 2018. He was also trained and excelled in mathematic modeling and programming for machine learning and represented CAU to compete in the National Mathematical Contest in Modelling. Supported by a joint program, he received research training in nutrition and immunology at the University of Wisconsin-Madison during his graduate study. Currently, he works as a Research Fellow in Wang Laboratory at MGH to study the etiology of carcinomas developed from the female reproductive tract and the subfertility/infertility associated with cancer treatment using genetically-modified animal models and customized in-depth (single-cell and spatial) transcriptomics. He is pursuing the establishment of an independent cancer-prevention research laboratory in the near future.

Jinpeng Ruan – Research Fellow

Dr. Ruan received his doctoral training at Xiamen University, where he studied the effects of environmental toxicants on reproductive and metabolic health using mouse models and cellular systems. He initially joined the Wang Lab as a visiting graduate student, spending a highly productive year and a half in the lab before completing his PhD in December 2024 and transitioning to his current role as a Research Fellow in January 2025. Dr. Ruan’s research focuses on developing and applying transgenic mouse models to investigate the cellular and molecular mechanisms of cancer development, with an emphasis on gynecologic malignancies. He has generated multiple novel models, including the first papillary renal cell carcinoma (pRCC) mouse model in collaboration with Dr. Lv (published in Nature Communications, 2025), as well as several gynecologic cancer models, including a uterine serous carcinoma model. His current research investigates the molecular crosstalk between the Hippo signaling pathway and oncogenic viruses, aiming to uncover how these interactions drive epithelial transformation and tumor progression in the female urogenital tract.

Xingeng (Vincent) Zhao, MS

Vincent earned his Bachelor of Science from the University of Waterloo joint with Beijing Jiaotong University in 2022. He studied physics and biophysics including electron energy levels and molecular orbital hybridization during his undergraduate training. He then attended Columbia University to study genetics in Tosches Lab and Firestein lab, and later obtained his master’s degree in 2024. In MGH, his current research focuses on exploring cellular and molecular mechanisms underlying high-grade serous ovarian cancer development using spatial transcriptomics.

Students

Olukemisola Abioye Adewunmi
Brianna Carbajal
Reema S. Guda
Kumar Gunjan
Ayan Ahmed Mohamed
Madelyn Leigh Moness
Isabelle Montoute
Samaya Saab

Publications

View publications

Open Positions

Perspective applicants are invited to contact the principal investigator to inquire about current or future opportunities.