Alexander "Sasha" Poltorak, Ph.D.
Immunology
Augusta University
Recruited: 2026
Alexander “Sasha” Poltorak explores how the body's first-line immune defenses sense bacteria, and how an infected cell decides whether to call for help through inflammation — or to sacrifice itself to stop the infection. These questions sit at the center of sepsis, inflammatory disease and autoimmunity. His lab looks for the genes behind these responses in wild-derived mice, strains far more genetically diverse than standard laboratory mice that retain gene functions lost by other lab strains.
Early in his career, Poltorak was lead author on the 1998 study that first identified the receptor in the body that allows the immune system to recognize a substance (LPS) found on many harmful bacteria. It was a historic advance in understanding how the body’s first line of defense against infection works. The paper has been cited more than 10,000 times and helped earn the Nobel Prize in Physiology and Medicine for Poltorak’s mentor, Bruce Beutler.
At Tufts, Poltorak’s lab described new ways that cell death and inflammation are wired together. He conducts research in the Immunology Center of Georgia at Augusta University; at Tufts, he chaired the Department of Immunology.
Research
- Identified the receptor the body uses to detect bacterial endotoxin. Endotoxin, also called LPS, is a molecule on the surface of many bacteria that sets off a powerful immune response. For decades, the sensor behind that response was unknown. Working in Beutler's lab at UT Southwestern Medical Center in Dallas, Poltorak was lead author on the 1998 study that traced endotoxin resistance in mice to a gene for Toll-like receptor 4 (TLR4).
The breakthrough showed that TLR4 sits at the heart of how the body detects infection and inflammation. Major advances in immunology followed, such as the discovery of families of immune-sensing genes and the approval of TLR-based drugs used in vaccines and skin treatments.
- Showed that a low, steady interferon signal readies immune cells for inflammatory cell death. Interferons are alarm proteins, and earlier work had tied necroptosis, an inflammatory form of cell death, to the interferon that bacteria provoke. Poltorak's lab found that in immune cells called macrophages, the small amount of interferon signaling present before any infection is what lets necroptosis get under way quickly. That background signal keeps a protein the cell needs in order to die above a critical level.
- Discovered a new trigger for pyroptosis, a kind of cell death that causes inflammation. In pyroptosis, a dying cell bursts open and releases alarm signals such as IL-1β. Scientists knew that two enzymes, caspase-1 and caspase-11, could start this process. Poltorak's lab showed that a third, caspase-8, can start it too, by cutting a protein called gasdermin D, which then punches holes in the cell's outer layer.
- Traced a deadly immune overreaction to two proteins. In sepsis, the body's response to an infection spins out of control and damages its own organs. A chemical messenger called TNF helps drive that overreaction. Poltorak's lab found that TNF does part of its harm through two proteins, TRIF and CD14, that immune cells normally use to detect bacteria. Mice lacking either protein had less organ damage after a lethal dose of TNF, and more of them survived.
Choosing Georgia
“During my first visit to the Immunology Center of Georgia (IMMCG), I was pleasantly surprised to see many young investigators enthusiastic about their research and aggressively applying for funding. This critical mass of immunologists, plus the internationally recognized leadership of Klaus Ley and Lynn Hedrick and the commitment of the university, were a factor in my decision. Also, cardiovascular research is a key component of the research at IMMCG, with several labs complementing activities of the others.”
