Fred Hutchinson Cancer Research Center scientist Dr. Amit Sharma, an investigator in the Hutch’s Human Biology Division, has received a Pathway to Independence Award from the National Institutes of Health.
The award will cover two years of mentored postdoctoral support in the lab of Dr. Julie Overbaugh, where he currently works, followed by two years of independent support designed to help Sharma set up his own lab. Funding for the $692,000 grant will come from the National Institute of Allergy and Infectious Diseases.
Only “highly promising candidates” have a shot at the four-year grants, according to the NIH. Sharma, who last fall was awarded a $150,000 fellowship from The Foundation for AIDS Research, said he will use the latest award to further his research in the realm of simian HIV-like viruses used in HIV vaccine experiments.
Sharma studied molecular genetics, virology and infectious diseases at The Ohio State University before coming to Fred Hutch in late 2013. In the Overbaugh Lab, researchers focus on understanding the mechanisms of HIV transmission and pathogenesis. Overbaugh’s team is working on developing a better HIV model, which researchers need to build a truly effective HIV vaccine.
Sharma’s research focuses on how HIV and other retroviruses interact, evade and overcome defenses of the immune systems and how these interactions can limit or allow transmission from one species to another. Understanding these host-virus interactions is particularly important in improving the “challenge” viruses used to test experimental vaccines before they are ready for human clinical trials.
Overbaugh, in her statement of support, said Sharma had “all the makings of a successful independent scientist,” referring to him as highly productive, collaborative and “always willing to help others in the lab.”
Sharma, in turn, was quick to credit Overbaugh for her help in securing the award.
“I am extremely grateful,” he said. “This award is another testament to Dr. Overbaugh's exceptional excellence in mentoring … She has helped me form close collaborations of my own, so that I can establish new research directions to build upon during my independent research career, and she is helping me outline the skills, training and other career development activities necessary to successfully transition to an independent academic position.”
Sharma said he was also thrilled to learn he’d received a perfect score of 10 on his grant application.
“That was the icing on the cake,” he said.
— Diane Mapes / Fred Hutch News Service
A new Fred Hutch study in mice suggests that in a tumor’s early stages ― long before a human tumor would be clinically recognizable ― certain immune cells can recognize initial changes that make it possible for these cells to behave as a cancer. Those immune cells never become fully able to launch an attack, as they are rapidly turned off and then permanently silenced, underscoring what a wily foe cancer can be against the immune system.
The study, published in the Aug. 9 issue of the journal Immunity, was led by Fred Hutch immunologist Dr. Phil Greenberg and Dr. Andrea Schietinger, a former postdoctoral research fellow in the Greenberg Lab who now heads an immunotherapy lab at Memorial Sloan Kettering Cancer Center.
Although our immune cells are trained early in development to not recognize and harm our own cells, cancerous cells bear many tumor-specific molecules, or antigens — which, in theory, could spur a potent immune response if the tumors weren’t able to block such a response. An outstanding puzzle in the immunotherapy field concerns the early stages of tumor development, in which cancerous cells acquire “driver” mutations in some of their genes. Such mutations are responsible for transforming a normal cell into a cancerous cell that can proliferate and invade tissues, but can change the appearance of the cells to the point that they could be recognized as foreign by the immune system. But to date researchers have had difficulty finding evidence that our immune cells actually recognize these very early stages of tumor formation.
“Our results highlight that driver mutations, which theoretically would be the most effective antigens to target because they represent the basis for a tumor behaving as a tumor, are not immunologically silent and can indeed be recognized,” said Greenberg.
The new study shows that certain immune cells, known as CD8+ T cells or killer T cells, can recognize such driver mutations but are quickly rendered nonfunctional, thereby protecting the tumor from an immune attack and allowing it to progress. If researchers could figure out a way to reverse that silencing, the strategies could be used to rescue the tumor-recognizing T cells to proceed to attack the tumor. This could improve the performance of certain immunotherapies, including that of so-called checkpoint-inhibitor drugs that release some of cancer’s brakes on the immune system. These inhibitors, such as the drug pembroluzimab, allow patients’ bodies to mount an immune response to mutations that have cropped up later in cancer’s progression, when the tumor is better established.
Greenberg and his research team are now pursuing two strategies to build off of their findings. One strategy focuses on defining the molecules that render the tumor-recognizing T cells dysfunctional. The ultimate goal is to disrupt those silencing molecules. The other strategy is to engineer, for eventual therapeutic use, T cells that recognize the driver mutations but cannot be shut off by the tumor.
― Rachel Tompa / Fred Hutch News Service
Dr. Janghee Woo, a senior oncology fellow at Fred Hutch, is one of 20 young investigators selected this year to participate in an international program in translational research, which aims to bring discoveries made at the laboratory bench to the bedsides of patients.
In addition to his work at Fred Hutch, Woo is a fellow in the Genome Sciences and Medicine laboratory of Dr. John Stamatoyannopoulos at the University of Washington. Woo specializes in disorders of blood cell production such as myelodysplastic syndrome and myeloproliferative neoplasms.
He was selected for the 2016 Translational Research Training in Hematology, or TRTH, a joint program sponsored by the American Society of Hematology and the European Hematology Association. “This gives me the opportunity to interact with very well-known international scientists,” said Woo. “It has already changed my project in a most valuable direction, and helped me to formulate the next step.”
Participants met in Copenhagen in June at the 2016 EHA Annual Congress, where they attended small-group mentoring sessions. Woo and the other 20 participants, including Fred Hutch’s Dr. Melinda Biernacki, will present the status of their projects in December at the 2016 ASH Annual Meeting in San Diego.
Woo’s main research goal is to identify genetic mechanisms that contribute to malignancies in the bone marrow, where blood-forming cells reside. Of particular interest is a mutation found in 10 to 30 percent of cases of acute myeloid leukemia and other hematologic malignancies. While mutations of a suspect gene are known to affect production of a single amino acid, researchers have yet to explain why recurrent mutations of the gene in question contribute to disease. Woo is working to solve that puzzle.
While earlier experiments have shown the deletion of the gene may cause these blood cancers in mice, Woo notes there are “many differences between humans and mice, and we still have no idea whether and how the mutation can contribute to the development of disease in human bone marrow cells." In his laboratory studies, he will apply precise genetic techniques known as genome editing to generate specific mutations in normal human blood-forming cells and determine whether these changes lead to the development of disease.
The TRTH program offers a rigorous, yearlong training and mentoring experience directed at helping junior scientists build successful careers in translational hematologic research. At Fred Hutch, Woo works closely on his project with blood disorders experts Dr. Joachim Deeg and Dr. Beverly Torok-Storb of the Clinical Research Division and biostatistician Dr. Ying Chen of Public Health Sciences.
— Sabin Russell / Fred Hutch News Service
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