In the Shen lab, we aim to understand the genetic, epigenetic and metabolic mechanisms of cancer evolution. Our research focuses on PTEN, a frequently mutated tumor suppressor gene in human cancer. We have generated a number of mouse models of tumorigenesis by knocking in distinct PTEN mutations originally identified in cancer patients. We also created transgenic mouse strains carrying mutant signaling molecules on the PTEN pathways that allow genetic rescue or further promotion of tumor development. These unique model systems, coupled with an innovative series of cellular and molecular approaches, enable systematic dissection of PTEN function in genome maintenance and tumor suppression. Our recent research has been extended to understanding how PTEN regulates tumor immunity. The overarching goal of our studies is to identify critical molecules and signaling pathways for the precision treatment of cancer patients, tailored to the genetic, epigenetic, metabolic, and immune signature of each tumor.
Wen H. Shen, Ph.D.,Principal Investigator
Dr. Shen obtained her Ph.D. from University of Illinois at Urbana-Champaign and her official training was in physiology and immunology. Her postdoctoral study at Columbia University has led her research to the field of cancer biology with a focus on tumor suppressor genes. While PTEN was known as a cytoplasmic protein to antagonize PI3 kinase, her work uncovered “nuclear PTEN” and revealed its function in maintaining chromosome integrity. Since then, PTEN has entered “the nuclear age” and been recognized as a “guardian of the genome”. Dr. Shen joined Weill Cornell Radiation Oncology in October 2009. Since then, Dr. Shen has led her research team to scrutinize the nuclear function of PTEN, which resulted in a number of findings that significantly expanded the PTEN tumor suppressive network. Dr. Shen is interested in collaborating with cancer biologists, immunologists and oncologists to implement cancer genetics-based translational studies to facilitate the effectiveness of combined radiotherapy and immunotherapy.
Meng Ouyang, M.D., Ph.D., Postdoctoral Associate
Dr. Ouyang graduated from Peking University, Beijing, China in 2014. He joined Dr. Shen's lab as a postdoctoral associate in the Department of Radiation Oncology in September 2015. His research focuses on the role of nuclear PTEN in maintaining mitotic chromosome stability. Dr. Ouyang utilizes a combination of live cell imaging, biochemistry, and gene editing approaches to study how PTEN deficiency impairs genetic transmission, leading to chromosome aberrations and aneuploidy.
Sheng-Qi Hou, Ph.D., Postdoctoral Associate
Dr. Hou received his Ph.D. degree from Peking Union Medical College, Beijing, China in June 2015. He came to Weill Cornell Medicine to conduct his postdoctoral research in the Department of Radiation Oncology in December 2015. His major academic interests are in the area of tumor immunity and he studies the role of PTEN in mediating the tumor-immune interplay. Using different Pten mutant mouse models, he focuses on characterization of the immune profile during tumorigenesis and identification of the molecular mechanisms that trigger tumor escape. Dr. Hou’s research goal is to facilitate translation of his research findings into improvement of cancer treatment.
Andrew Brandmaier, M.D., Ph.D., Resident in Radiation Oncology
Holman Research Pathway
Dr. Brandmaier received an MD/PhD from Indiana University in 2012 and has prior research experience in the areas of melanoma, tumor immunology and immune tolerance. He is currently a fellow in the Holman Research Pathway collaborating with Dr. Shen and Dr. Demaria in the laboratory of Radiation Oncology at Weill Cornell Medical Center. His project is investigating the role of PTEN in directing the proliferation and phenotype of tumor infiltrating regulatory T cells. The goal of his current research is to discover new therapeutic approaches that can favorably modulate T cell responses in combination with radiation therapy to enhance anti-tumor immunity.
Hongbo Hao, M.S., M.D., Research Associate
Dr. Hao earned her medical degree from China Medical University. She obtained research training and her M.S. degree at Chinese Academy of Medical Sciences. In 2006, Dr. Hao became a physician in Hematology/Oncology and her primary specialty has been in malignant hematologic diseases. Dr. Hao came to Weill Cornell Medicine in August 2014 to advance her research experience and she joined the laboratory of Dr. Shen as a research associate. She plays an essential part in multiple basic and translational projects using PTEN-deficient model systems.
- Sun, Z., et al. PTEN C-terminal deletion causes genomic instability and tumor development. Cell Reports. 6:844-854. Mar 2014.
- Liang, H., et al. PTENα, a PTEN isoform translated through alternative initiation, regulates mitochondrial function and energy metabolism. Cell Metabolism.19:836-848. May 2014 (Cover Story).
“Giving mitochondria a boost with PTENα” Science Signaling. 7: ec143. May 2014.
“(P)TEN-ding to mitochondria” Nature Reviews Molecular Cell Biology. 15:366-367. Jun 2014.
- Chen, Z.H., et al. PTEN interacts with histone H1 and controls chromatin condensation. Cell Reports. 8:2003-2014. Sep 2014.
“Chromatin: Interplay of PTEN with histone H1” Nature Reviews Molecular Cell Biology. 15:630. Oct 2014.
- He, J., et al. PTEN regulates DNA replication progression and stalled fork recovery. Nature Communications. 6:7620. Jul 2015.
- Kang, X., et al. PTEN stabilizes TOP2A and regulates the DNA decatenation. Scientific Reports. 5:17873; Dec 2015.
- Yu, S., et al. Genome maintenance in the context of 4D chromatin condensation. Cellular and Molecular Life Sciences. 73:3137-3150. Aug 2016 (Cover Story).
- He, J., et al.PTEN regulates EG5 to control spindle architecture and chromosome congression during mitosis. Nature Communications. 7:12355. Aug 2016.
- Zhang, et al. PTEN regulates PLK1 and controls chromosomal stability during cell division. Cell Cycle. 15:2476-2485. Sep 2016.
“Unmasking PTEN's nuclear functions” Cell Cycle. 15:3341-3342. Dec 2016.
- Brandmaier A., et al. PTEN at the interface of immune tolerance and tumor suppression. Frontiers in Biology. 12:163-174. Jun 2017 (Cover Story).
- Brandmaier, A., et al. Cell cycle control by PTEN. Journal of Molecular Biology. pii: S0022-2836(17)30290-5. [Epub ahead of print] Jun 2017.
- Hou, S.Q., et al. PTEN in the maintenance of genome integrity: from DNA replication to chromosome segregation. BioEssays. (Invited review, manuscript under review)
Lab address: 525 East 68th Street, Whitney 212, New York, NY 10021
Lab phone number: 212-746-3996
PI office: 525 East 68th Street, Whitney 204, New York, NY 10021
Office phone number: 212-746-1678