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Inder M. Verma

 

Inder M. Verma

Inder M. Verma

Professor, Irwin and Joan Jacobs Chair in Exemplary Life Science
Laboratory of Genetics

"One of the major interests in our laboratory is to understand the process of inflammation, which is the underlying cause of many diseases."

When our bodies come across an allergen (such as pollen), specialized cells called mast cells discharge a burst of histamine at the site of the encounter—an important weapon in the body's arsenal for fighting allergic reactions. In people with allergic diseases, histamine is released throughout the body, leading to severe inflammation and in the worst cases, anaphylactic shock and death. Inside mast cells, histamine is bundled into membrane-bound sacs called vesicles, which transport it to the cell surface when needed. Once the vesicles reach the surface, they fuse with the outer membrane of the cell, spilling their contents into the extracellular space in a process known as exocytosis.

Trying to uncover the molecular mechanism that in most people prevents this process from going overboard, Verma and his team zoomed in on the role of IKK2. This enzyme activates NF-kB, a genetic switch that regulates gene expression and was already known to be involved in other types of immune responses. Indeed, mice with mast cells lacking IKK2 had reduced allergic reactions since they couldn't release enough histamine. But IKK2's role in the allergic response does not stop there—it multitasks. After the rapid "early phase" exocytosis response, mast cells undergo a "late-phase" reaction, during which certain genes are turned on to help fight the allergen. Verma found that the late-phase response also requires IKK2, making it an ideal target for the development of allergy drugs.

Verma's lab is now testing inhibitors of IKK2 as acute treatment for allergic reactions. Unlike antihistamines, which are currently used to combat allergies, IKK2 inhibitors would have the added benefit of reducing both the early- and late-phase allergic responses. The newly discovered role for IKK2 may not be limited to allergic reactions. Many fundamental processes in our bodies involve exocytosis, ranging from secretion of insulin in the pancreas to the transmission of signals between nerve cells. If IKK2 is involved in these processes as well, it may have a role in other pathologies such as diabetes and nervous system diseases.

Lab Photo

Left to right:
Top row: Tatiana Hurtado De Mendoza, Eugene Ke, Oded Singer, Nils-Bjarne Woods, Mark Schmitt
Next row down: Karl-Dimiter Bissig, Dinorah Morvinski, Aaron Parker, Tomotoshi Marumoto
Next row: Yasushi Soda, Rajesh Narasimamurthy, Quan Zhu, Gerald Pao Next row: Beth Coyne, Kotaro Suzuki, Gabriela Estepa, Simone Ward, Samantha Serey, Nien Hoong, Inder Verma, Fei Liu
Front row: Yifeng Xia, Nina Tonnu, Mie Soda

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Inder M. Verma

Faculty

Inder M. Verma

Inder M. Verma

Professor, Irwin and Joan Jacobs Chair in Exemplary Life Science
Laboratory of Genetics

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.

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