Salk Institute
Inder M. Verma
Professor
Laboratory of Genetics
American Cancer Society Professor of Molecular Biology
Irwin and Joan Jacobs Chair in Exemplary Life Science
Inder M. Verma

Professor
Laboratory of Genetics
American Cancer Society Professor of Molecular Biology
Irwin and Joan Jacobs Chair in Exemplary Life Science


Research

Inder M. Verma, a professor in the Laboratory of Genetics and American Cancer Society Professor of Molecular Biology, is one of the world's leading authorities on the development of viruses for gene therapy vectors. Dr. Verma uses genetically engineered viruses to insert new genes into cells that can then be returned to the body, where they produce the essential protein whose absence causes disease.

Dr. Verma and Salk colleagues developed a gene therapy vector, based on a stripped-down version of HIV, that can deliver genes to non-dividing cells, which constitute the majority of the cells in our bodies. They have used this vector successfully to deliver the clotting factor gene to laboratory animals and to transfer a therapeutic gene to retinal cells to mice with an inborn deficiency. Dr. Verma's group is also studying two genes implicated in familial breast cancer, BRCA1 and BRCA2, and recently demonstrated that their action is linked to the cell's division cycle and that BRCA1 regulates gene activity.

"One of the major interests in our laboratory is understanding the molecular mechanisms of cancer and the role of inflammation, which is the underlying cause of many diseases."

The mouse has long provided researchers with valuable insights about cancer. But the most commonly used technique for producing a cancer mouse model–transplanting human tumor tissue or cancer cell lines in immunocompromised mice– ignores the role of the immune system in cancer. Other animal models either express oncogenes in a tissue-specific manner or shut down the expression of tumor suppressor genes in the whole tissue. But tumors generally develop from a single cell or a small number of cells of a specific cell type, which is one of the major determinants of the characteristics of tumor cells.

To create a better mouse model, researchers in Verma's laboratory turned to gene therapy techniques, using modified viruses to infect cells and ferry activated oncogenes into a small number of cells in adult, fully immunocompetent mice. After initial experiments confirmed that the approach was working, his team injected viruses carrying two well-known oncogenes into three brain regions of mice lacking one copy of the gene encoding the tumor suppressor p53. They specifically targeted astrocytes, star-shaped support cells that are suspected of being the source of glioblastoma, the most common and deadly human brain cancer. Within a few months, massive tumors that displayed all the histological characteristics of glioblastoma developed in two of the regions.

To test whether the induced glioblastomas contained cancer stem cells, investigators isolated and cultured individual tumor cells in the lab, which looked and behaved just like neural stem cells. Less than 100 and as few as 10 cells were enough to initiate a tumor when injected into immunodeficient mice. These findings show that this cancer model will not only allow scientists to gain new insights into the biology of glioblastoma but will also help them answer many questions surrounding cancer stem cells. Verma and his team are currently using this methodology to investigate lung and prostate cancers.

Verma's lab is also exploiting the technologies developed for gene therapy to generate induced pluripotent stem cells (iPCs) from patients and converting them into hematopoietic stem cells, hepatocytes and lung cells.

Lab Photo

Standing, left to right: Junko Ogawa, Yifeng Xia, Rajesh Narasimamurthy, Chad Myskiw, Elisa Nigro, Amy Firth, Gabby Estepa, Dino Morvinski, Beth Coyne, Tatiana Hurtado De Mendoza, Quan Zhu, Nina Tonnu, Susan Qualls, Fei Liu, Amy Rommel, Suvasini Ramaswamy

Seated, left to right: Suneer Verma, Martin Preyer, Yasushi Soda, Nien Hoong, Ruben Alvarez, Inder Verma, Narayana Yeddula, Mark Schmitt, Eugene Ke, Tushar Menon, Gerald Pao

Salk News Releases

Awards and Honors

  • NIH Outstanding Investigator Award, 1988
  • The Third World Academy of Sciences
  • National Academy of Sciences
  • March of Dimes Birth Defects Foundation Franklin D. Roosevelt Investigator, 1997
  • Institute of Medicine
  • President, American Society for Gene Therapy, 2000-2001

Discovery links breast cancer gene to brain development

April 7, 2014


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