Building better tools to probe the immune response

Dr. Ranit Kedmi, who joined the Department of Systems Immunology as a Principal Investigator in early 2023, grew up in a science-friendly home, yet as a child, she never imagined herself as a scientist.

While her initial inclination led her to pursue a double major in law and business administration, in 2000, while she was still a law student, an international consortium of scientists cracked the human genome. Fascinated, she began reading one popular science book after another. When sheer curiosity propelled her from popular science to academic texts, she decided science was her calling.

She earned a BSc cum laude from Tel Aviv University, following it with an MSc in biology from the Weizmann Institute of Science, under the supervision of Prof. Rivka Dikstein in the Department of Biomolecular Sciences. For her PhD, Dr. Kedmi returned to Tel Aviv University, studying nucleic acid delivery and nanotechnology. Her thesis focused on an aspect of developing a universal delivery platform for regulatory RNAs. This technology made global headlines when pharmaceutical giant Pfizer developed its SARS-CoV-2 vaccine, although her personal project focused on targeted delivery.

As a postdoctoral fellow at New York University School of Medicine, Dr. Kedmi specialized in immunology in the lab of Prof. Dan Littman, where she studied the subsets of antigen-presenting cells (APCs)—immune cells that “show” antigens (foreign molecules, particulates, or allergens) on their surface to other immune cells— needed to initiate distinct T cell programs in response to various gut microbiota.

When the immune response functions properly, a subtype of white blood cells called CD4+ T cells recognize antigens and switch from a passive to an active state, triggering immune cells to produce antibodies that destroy the harmful antigens. A malfunctioning immune response, however, can lead to all manner of disease, including conditions that were historically not linked to immune defects, such as neurodegenerative illnesses and cancer.

“In the process of activation, the T cells acquire programs that control which immune response will occur. As soon as the T cells become one thing rather than another, they can ‘talk’ to different cells, enlist different cells,” Dr. Kedmi says.

“My main goal is to try and understand immunity through the lens of antigen presentation, to understand what plays a part in the immune response—which instructions are transmitted, and which instructions are received. I want to understand the network.”

T cells are, in a way, plastic. “If you take a T cell that is in program X and transfer it to a mouse where an antigen can be expected to lead to program Y, it changes. It ‘listens’ to instructions from its environment,” she explains.

Constant crosstalk

According to Dr. Kedmi, most immune-related illnesses, which account for most human diseases, entail “non-optimal responses” in which CD4+ T cells execute different programs than they should, making the question of how T cells select their program critical. Part of the answer came from 2011 Nobel Prize laureate Ralph Steinman, who discovered dendritic cells, which present antigens as well as issue signals to T cells, essentially telling them what to target.

For years, immunologists have been trying to understand whether dendritic cells have a single “general setting” that senses different antigens and deploys the appropriate T cell response, or whether there are different types of antigen-presenting cells. Dr. Kedmi’s research indicates unequivocally that multiple types of APCs create specific immune responses. She and her team also discovered a heretofore overlooked tiny population of cells distinct from the classic dendritic cells Steinman identified.

Dr. Kedmi explains that there is “constant crosstalk” between APCs and T cells that have the right “key,” which, in turn, develops into a specific response to a given antigen. T cells that acquire the program “teach” other cells, such as B cells—a type of lymphocyte 

that develops in the bone marrow—to create antigens through a program called T follicular helper cells (TFH).

She believes that antigen presentation, which not only initiates the CD4+ T cells but also allows them to operate, is the “beating heart of adaptive immunity.”

The regulators

As a postdoc at NYU, Dr. Kedmi worked on a cutting-edge immunological model that allowed her and her colleagues to track immunological responses to different triggers. They identified the cells that instruct naïve T cells to adopt an immune program called “regulatory T cells” (Tregs). Tregs, along with TFH, are key to immune tolerance, the loss of which is a major component of autoimmune disorders.

Dr. Kedmi strives to use RNA delivery to lead antigens to certain cells that cause a Treg response, reversing a loss of tolerance.

“Now that we’ve discovered that there are cells that cause a Treg response, we can’t not try employ RNA delivery to lead antigens to them to see if we can initiate tolerance,” she says. An effective version of this technology could turn into a platform to treat a multitude of diseases: “Allergies, autoimmune disorders, neurodegenerative diseases. But it’s still in its infancy.”

At the Weizmann Institute, her first priority is using her engineering capabilities to develop new tools and methods that will make it possible “to observe all this at a much higher resolution.”

Dr. Kedmi is married and has four children. She is passionate about her work and committed to fostering a happy, supportive, and diverse group both in her lab and in the broader scientific community.

“When science comes from new and unexpected directions, it adds to the creativity and color. There used to be a lot of glass ceilings—you had to do X to get to Y. I think that’s a path that leads very specific people to the top, and it’s a loss for science for them to be the only ones there,” she says.

Education and select awards

• LLB in law, BA in business administration, Interdisciplinary Center Herzliya (now Reichman University) (2003)

• BSc cum laude, Tel Aviv University (2004)

• MSc, Weizmann Institute of Science (2007)

• PhD, Tel Aviv University (2014)

• Postdoc, New York University School of Medicine (2016-2022)

• Legacy Heritage Stem Cell Fellowship (2008); KAMIN technology transfer program from the Chief Scientist’s Office (2013); Prize for scientific excellence, European Foundation for Clinical Nanomedicine Conference (2015); Cancer Research Institute/Irvington Fellow (2018-2020); Cancer Research Institute/ Robertson Foundation Postdoctoral Fellowship (2017-2021)