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The UNC School of Medicine selected Joe Eron, MD, professor of medicine and vice chief for the division of infectious diseases, and Brian Kuhlman, PhD, professor of biochemistry and biophysics, as Oliver Smithies Investigators, an annual award to honor senior faculty members who have made significant research contributions and achieved international recognition for their work.

Eron, a member of the UNC Institute for Global Health and Infectious Diseases, is the Director of the Clinical Core for the UNC Center for AIDS Research and adjunct professor of epidemiology at the UNC Gillings School of Global Public Health. Kuhlman, a member of the UNC Lineberger Comprehensive Cancer Center, is the co-director of the UNC Molecular and Cellular Biophysics Program.

photo of Joe Eron MD and Brian Kuhlman PhD
Joe Eron MD and Brian Kuhlman PhD

The Smithies Investigator Award was established in honor of the research achievements of UNC Nobel Prize Winner Oliver Smithies, DPhil, the late Weatherspoon Eminent Distinguished Professor in the Department of Pathology and Laboratory Medicine.  Smithies Investigators receive $75,000 for research over a five-year term, become members of the Oliver Smithies Society, and will present highlights of their research accomplishments at a special seminar in 2019.

Eron is internationally recognized for his groundbreaking contributions to the global care of patients with HIV infection and locally known for the personal level of expert care he gives patients in North Carolina. Eron’s work in HIV included the first study demonstrating substantial activity of combination antiretroviral treatment of HIV in a randomized clinical study, published in the New England Journal of Medicine in 2005. He followed this advance as one of four investigators leading the first clinical trial of the HIV ‘cocktail’ that led to the dramatic change in HIV treatment and care. He has led or collaborated on numerous subsequent studies leading to the development of new antiretroviral agents and improved combination antiretroviral therapy.

Through his work on novel antiretroviral agents, combination antiretroviral therapy, and our understanding of HIV resistance and transmission, he has been a major contributor to our current effective treatment of this previously deadly disease. Through Eron’s leadership, the UNC research team and HIV patients in North Carolina have participated in these studies, improving the treatment of HIV patients in the United States and worldwide. This high-level research has led to HIV becoming a disease that is survivable, rather than a death sentence.

Eron has made significant contributions to more than 400 published manuscripts, including many as first or senior author. He is an academic leader in translational medicine, a scientific leader in the field of HIV research, a compassionate clinician, and valued teacher and mentor at the UNC School of Medicine

Kuhlman’s research has made enormous fundamental contributions to the field of protein design. He is one of the principal developers of the molecular modeling software Rosetta, developed for the design and prediction of macromolecular structures. To date more than 25,000 academic and government users have obtained licenses for Rosetta, the software of choice for protein designers. In the last four years, authors of more than 30 papers in the journals NatureScience, and Cell made critical use of Rosetta for a variety of tasks including epitope-focused vaccine design and the design of new antibody formats for fighting cancer.

Kuhlman has made seminal discoveries in the field of de novo protein design. He was the first scientist to design and experimentally validate a protein fold not previously seen in nature. The paper describing this work won best paper of the year in 2003 in Science and earned him the AAAS Newcomb Cleveland Prize. More recently, his lab developed a new method for protein design that stitches together pieces of naturally occurring proteins to create a large and diverse set of protein conformations. His lab is now using this technology to create protein inhibitors, biosensors, and ligand binding proteins.

Kuhlman’s group has been collaborating with Eli Lilly to create bispecific antibodies that have all the beneficial properties of monoclonal IgG antibodies but can recognize two antigens simultaneously. Bispecific antibodies can be used to induce immune cells to kill cancer cells. This work has generated several new bispecific antibody platforms Kuhlman has patented, and Eli Lilly has started several clinical trials with molecules built on this bispecific antibody platform.

In the emerging field of optogenetics, where light is used to activate cell signaling events, Kuhlman’s group used a combination of computational design and high-throughput screening to build an optogenetic switch that controls G protein signaling with sub-cellular resolution. The genes for this switch are now available through Addgene. Within the last year, over 460 samples were distributed to laboratories around the world.

Kuhlman’s former trainees have gone on to spectacular careers in industry, government, or structural biology labs at Harvard, MIT, and Rutgers. And each spring, starting in 2005, he teaches a structural bioinformatics course that has grown in popularity among first-year graduate students, more than a third of whom take Kuhlman’s course.

The late Oliver Smithies, who was a faculty member at UNC-Chapel Hill for more than 25 years, won the Nobel Prize in Physiology or Medicine in 2007. He co-discovered a technique he called “gene-targeting,” which allows scientists to study genetic mutations by knocking out specific genes in mice. The method became ubiquitous in basic research labs and opened up a new kind of scientific inquiry into many different diseases.

Story courtesy of Mark Derewicz, UNC Healthcare