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Two 51��Ʒ��Ƶ investigators have received the prestigious National Institutes of Health (NIH) Director’s to support unconventional approaches to major challenges in biomedical and behavioral research.

Alok Joglekar, assistant professor at the Center for Systems Immunology and the Department of Immunology in the , and Tagbo Niepa, assistant professor of chemical and petroleum engineering in the , will receive a total of more than $4 million in support of their scientific research projects. As part of the NIH’s , the awards recognize exceptionally creative early career scientists pursuing unusually innovative research.

“This award has enormous value because it funds big ideas that are early in development but hold potential for high impact,” said Joglekar. “For early stage investigators like myself, this support is incredibly important because it allows us to dive head-first into these ideas and gives us a cushion for taking risks and innovating.”

Tweaking T cells

focuses on engineering molecules to manipulate T cells of the immune system to boost tumor-killing prowess in cancer or suppress them from attacking healthy tissues in autoimmune diseases.

T cells respond to pathogens, good microbes and the body’s own cells when T cell receptors recognize unique antigens that are displayed on MHC (major histocompatibility complex) molecules. Usually this is a “one-way street” with T cells responding to target cells, but Joglekar and his team have engineered MHC molecules to have signaling components, creating a new class of molecules called SABRs. When engineered to bear SABRs, immune cells can respond to T cells and manipulate their function.

“We’ve essentially converted a one-way street into a two-way,” Joglekar said. “We know that the concept works, and in the next five years we want to establish preclinical studies that we hope will eventually lead to new treatments for autoimmune diseases such as type 1 diabetes and multiple sclerosis and enhance immunotherapies for tumors. We also hope to use this platform to tweak specific functions of the immune system to understand it better.”

The microbiome as medicine

Niepa, who runs the , has been recognized for his research toward developing capsules that aim to restore the microbiome after it is disrupted by infections or other illnesses.

The to mimic conditions in a microbe’s natural environment, facilitating the growth of previously difficult to culture species and avoiding growth biases that occur in traditional cultures when different microbes are competing for space and nutrients.

“With this technology, we can actually collect and store samples from healthy individuals, screen them to understand the composition of their microbiome and later administer to the patient when they’re sick,” said Niepa.

One target for the capsules is people who have contracted Clostridium difficile, or C. diff, a bacterium that causes serious intestinal problems and often eliminates good gut bacteria. One day, thanks to Niepa’s research, simply swallowing a pill could restore gut balance and promote a healthy microbiome.

“If this project is successful, it could mean a huge shift in the way we think about illness and medicine,” said Niepa. “This work creates a necessary framework for future research into the manipulation of the human microbiome to prevent and even cure disease.”

The NIH grant numbers are DP2AI176138 (Joglekar) and DP2GM14955 (Niepa).

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— Asher Jones and Maggie Lindenberg