Faculty

Chengcheng Jin

faculty photo
Assistant Professor of Cancer Biology
Department: Cancer Biology
Graduate Group Affiliations

Contact information
421 Curie Blvd
Rm 706, BRB II/III
Perelman School of Medicine
University of Pennsylvania
Philadelphia, PA 19104-6160
Office: 2157461764
Education:
B.S. (Biological Science)
Tsinghua University, Beijing, China, 2007.
Ph.D. (Cell Biology)
Yale University, New Haven, CT, 2013.
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Description of Research Expertise

Research area:
The pathogenesis of cancer involves not only intrinsic genetic alterations in tumor cells but also the failure of immune surveillance and unresolved inflammation. However, it is not well understood how host-intrinsic or environmental factors direct the immune response towards tumor-promoting inflammation versus anti-tumor immunity during tumor progression. In particular, mucosal surfaces exposed to the external environment are colonized by a vast number of microbes, collectively referred to as the commensal microbiota. Our work and the work of others have just begun to unveil the critical role of commensal microbiome in shaping the tumor microenvironment (TME) at the mucosal sites to regulate the tumor-immune interactions. This is as an area of tremendous opportunity for significant breakthroughs in cancer research.

The research at our lab lies at the forefront of: (1) Understanding how immune responses are initiated and evolve over time as tumors arise de novo and progress in the native TME; (2) Defining the molecular and cellular mechanisms by which the immune system senses and responds to microbiota-derived or tumor-intrinsic signals in the TME to regulate tumor growth and responses to therapies.

We are combining multi-omics approaches, advanced imaging and mouse genetic models to address the fundamental questions in cancer immunology and mucosal immune-microbiota interaction. Findings from our research will not only advance our understanding of the fundamental immunobiology of tumorigenesis, but also provide critical insights into novel strategies for cancer prevention and treatment.

Current projects:
1. Elucidate the impacts of local and distal microbiota on tumor-associated immune responses in the lung.
Our current understanding about microbiota and cancer has been mostly limited to the intestinal microbiota. As a mucosal organ harboring the largest surface area in the body, the lung is exposed to a variety of air-borne microbes and also colonized by a diverse bacterial community in both physiological and pathological conditions. We have established various experimental tools to analyze and manipulate lung microbiota, and revealed their changes associated with tumor progression. Moving forward, we are working to further (1) elucidate the cellular and molecular components of the lung or intestinal microbiota that shape the TME in a spatial-temporal fashion; (2) understand how they orchestrate the balance between tumor-promoting inflammation and anti-tumor immunity to regulate tumor growth and response to therapies.

2. Reveal the spatial-temporal interactions between tumor and immune cells during cancer initiation and progression.
While intensive efforts in the field have been focused on tumor-immune interaction in established tumors, there is a critical gap in our knowledge about immune recognition and activation upon early oncogenic transformation, and about the co-evolution of immune cell populations with tumor cells during cancer progression. We have established genetically engineered mouse models that enable us to define the immune components of TME over the course of oncogenesis from nascently transformed cells to a full-blown tumor. Based on this system, we will take combinatorial approaches to perform a spatial-temporal analysis of tissue/tumor-infiltrating immune cells in regular and germ-free settings. Our goal is to understand the following long-standing questions in cancer immunology: (1) What types of immune cells interact with tumor cells at different stages of cancer development? (2) For a certain type of immune cells, do they function consistently from early to late stage, in the presence or absence of microbiota, or do they exhibit functional diversity and plasticity?

3. Define the host-intrinsic factors that shape the tumor immune microenvironment.
In addition to commensal microbiota, host-intrinsic factors are also critical in triggering immune recognition and activation in TME. While malignant transformation of epithelial cells leads to a dramatic change in their gene expression program over time and may thereby disrupt the normal immune-epithelial crosstalk, various damage or stress-associated molecules have also been implicated in the induction of innate immune response. Therefore, the goal of this project is to identify these host-intrinsic immuno-modulatory factors expressed from tumor cells or generated in the TME. We are integrating knowledge gained from the unbiased, genome-wide analysis of immune cells with the transcriptomic data of tumor cells at different time points of tumor development, and spearhead efforts in building signaling circuits and networks involved in epithelial-immune communication in a spatial-temporal fashion. Moreover, we will take advantage of the human cancer database to identify recurrent genetic alterations associated with human lung cancer, and examine how they influence tumor-immune interaction.

Altogether, we are broadly interested in understanding the mechanisms by which oncogene-driven molecular signatures, antigenic load, distinct tissue milieu and the local microbial compartment dictate the tumor-associated immune responses, and how we can target these mechanisms for more effective cancer therapies.

Selected Publications

Wong-Rolle A, Dong Q, Zhu Y, Divakar P, Hor JL, Kedei N, Wong M, Tillo D, Conner EA, Rajan A, Schrump DS, Jin C, Germain RN, Zhao C: Spatial meta-transcriptomics reveal associations of intratumor bacteria burden with lung cancer cells showing a distinct oncogenic signature. Immunotherapy Cancer 10(7), July 2022.

Arlova A, Jin C, Wong-Rolle A, Chen ES, Lisle C, Brown GT, Lay N, Choyke PL, Turkbey B, Harmon S, Zhao C: Artificial Intelligence-based Tumor Segmentation in Mouse Models of Lung Adenocarcinoma. Pathology Informatics January 2022.

Dong Q, Chen ES, Zhao C, Jin C* *Corresponding author: Host-Microbiota Interaction in Lung Cancer. Frontiers in Immunology May 2021 Notes: Review.

Hu B*, Jin C*, Zeng X*, Resch JM, Jedrychowski MP, Yang Z, Banks AS, Lowell BB, Mathis D, Spiegelman BM *Equal contribution: γδ T cells and adipocyte IL-17RC control fat innervation and thermogenesis. Nature 578(7796): 610-614, February 2020.

Wong-Rolle A, Wei H, Zhao C, Jin C* *Corresponding author: Unexpected guest in the tumor microenvironment: microbiome in cancer. Protein & Cell 2020.

Jin C, Lagoudas G, Zhao C, Bullman S, Bhutkar A, Hu B, Mazzilli S, Ameh S, Sandel D, Liang X, Whary M, Meyerson M, Germain R, Blainey P, Fox J, Jacks T: Commensal Microbiota Promote Lung Cancer Development via γδ T Cells. Cell 176(5): 998-1013, February 2019.

Hu B*, Jin C*, Li HB*, Tong J, Ouyang X, Zhu S, Strowig T, Lam FC, Zhao C, Henao-Mejia J, Fitzgerald KA, Eisenbarth SC, Elinav E, Flavell RA *Equal contribution: The DNA Sensing Aim2 Inflammasome Controls Radiation Induced Cell Death and Tissue Injury. Science 354(6313): 765-768, November 2016.

Jin C: Immunosurveillance of Tumors. Encyclopedia of Cancer 2015.

Li HB*, Jin C*, Chen Y, Flavell RA *Equal contribution: Inflammasome Activation and Metabolic Disease Progression. Cytokine & Growth Factor Reviews 25(6): 699-706, December 2014 Notes: Review.

Elinav E*, Nowarski R*, Thaiss C*, Hu B*, Jin C*, Flavell RA *Equal contribution: Inflammation-Induced Cancer: Crosstalk Between Tumours, Immune Cells and Microorganisms. Nature Reviews Cancer 13(11): 759-771, November 2013 Notes: Review.

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Last updated: 12/15/2023
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