Building the Next Generation of Translational Investigators

(LtoR): Françoise Barré-Sinoussi, PhD, winner of the 2008 Nobel Prize in Medicine for the discovery of HIV and Christina Gavegnano, PhD, post-doctoral fellow, Emory University

Clinical and translational research requires a specialized skill set and knowledge of a complicated pipeline. Team science is a critical component to success and no one person can be an expert in the process from start to finish. The Atlanta Clinical & Translational Science Institute (ACTSI) provides the network for translating the pipeline and the educational tools to build the specialized skills needed for success.

A clinical and translational research training program proving its value is the ACTSI’s Certificate Program in Translational Research (CPTR) – ideal for an investigator looking to gain the skills to translate their findings from the laboratory to the bedside and into the community.  The CPTR is a multidisciplinary program for PhD students, postdocs, residents, fellows, and faculty who seek to conduct research at the interface between basic science and clinical medicine.

“Despite the explosive growth in biomedical knowledge, it is increasingly difficult to translate this knowledge and discovery into applications that benefit human health. There is an urgent need to facilitate the translation of biomedical knowledge to improve health and address the gap between biology and medicine,” said ACTSI Principal Investigator, David Stephens, MD, vice president for research, Woodruff Health Sciences Center and Stephen W. Schwarzmann Distinguished Professor of Medicine at Emory University. “This starts with educating our young scientists. The ACTSI CPTR enhances and transforms translational research training for PhD students at Emory University, Georgia Institute of Technology, and Morehouse School of Medicine.”

Funded in part by the Howard Hughes Medical Institute, the certificate program (which can be completed in one or two years) is part of Emory’s Laney Graduate School. Henry Blumberg, MD, ACTSI’s Research Education, Training & Career Development (RETCD) program director and professor of Medicine (Infectious Diseases), Epidemiology, and Global Health, Emory University School of Medicine explains, “The program includes both didactic training and an experiential rotation that is part of the Translation to Clinical Medicine course which links a trainee in the program to a clinician investigator in the trainee’s field of interest. The CPTR also includes courses on clinical and translational research, epidemiology, biostatistics, ethics, grant writing, and community-based participatory research and participation in a Journal Club and IRB Rotation.”

For recent certificate graduate and post-doctoral fellow, Christina Gavegnano, PhD, the program was a way to bridge her basic science background, as a PhD student studying Pharmacology and working in Raymond Schinazi’s renowned HIV and drug discovery lab, and her clinical/drug discovery future. She has a master’s in Immunology and during her first PhD rotation she worked in Schinazi’s ACTSI-supported lab and never left.

In the early 1990s, Raymond Schinazi, PhD, ACTSI investigator, senior career research scientist, Atlanta VA and Frances Winship Walters Professor, Emory University School of Medicine, co-developed the molecules 3TC and FTC, which helps to prevent or delay HIV from replicating and infecting other cells. After continued work, 3TC/FTC are now taken by 94% of adults in the U.S. being treated for HIV, and as Atripla, the drug combination is the most popular and effective one-pill, once a day HIV therapy. “Joining Dr. Schinazi’s lab was the first step to working on a drug that has the implication to do something, because this is a lab with a strong track record,” said Gavegnano. By enrolling in the CPTR she knew she could see 3TC/FTC at work, in patients. “I had never seen a clinic setting or knowingly seen an HIV-infected person despite the fact that I have been working in HIV research since 2001.”

Gavegnano’s PhD work kept her in labs with no glimpse of the clinical side of medicine or patient contact. The certificate program offers the semester long course, Translation to Clinical Medicine, taught by Vin Tangpricha, MD, PhD, ACTSI investigator, associate professor of Medicine, Emory University School of Medicine. “Many of the students in the program have never been in contact with a patient in a clinical research setting. The course provides students a mentored clinical experience that is closely tied to the student's basic research project,” said Tangpricha. Gavegnano asked to be placed in a clinic treating HIV/AIDS patients. Her clinical preceptor was David Rimland, MD, ACTSI investigator, chief, Infectious Diseases, VA Medical Center (VAMC) and director, VAMC HIV Program, professor of Medicine, Emory University School of Medicine, and she was placed in his HIV clinics at the VAMC. It was emotional for Gavegnano to see her work in action. “The information from the CPTR applies to my real life. The translational process is no longer a mystery,” said Gavegnano.

For Gavegnano the program was a true translation from basic to clinical science. She was able to see her work come to life through the patients in Rimland’s clinic and brought what she learned to the lab. Her thesis focused on the development of a drug that she and Schinazi now hold the patent for, a JAK inhibitor for HIV. She is hopeful that the drug is able to do something novel relative to immunomodulator-based therapy. All of the drugs that are FDA approved target a step in the replication cycle of HIV and those drugs cannot eradicate HIV for a variety of reasons most notably related to immunological and inflammatory factors. “We are using the JAK inhibitors to attempt to understand if down regulating inflammation, which we believe modulates pro-HIV events, can in turn result in a functional cure or a step towards eradication,” said Gavegnano. This class of drug is currently approved by the FDA for the treatment of myelofibrosis and rheumatoid arthritis. No FDA-approved HIV drug on the market decreases inflammation like this one. “To have a drug moving forward into a clinical trial in HIV infected persons for me that is very exciting. I know that would not be the case if I weren’t here and through the CPTR I learned an immense amount that taught me about what’s going to happen to this drug and I wouldn’t have known that otherwise.” She wanted to know what happens on the back end of drug development. The front end – she knew about the research – the R&D, getting it all the way through pre-clinical, but knew nothing about what happens after that and the CTPR showed her step-by-step.

Her mentor, Dr. Schinazi supports Christina’s hypothesis. He stated, "Christina demonstrates a lot of imagination, maturity, and knowledge as well as a rare perceptive mind. She is motivated, determined, and driven. These qualities should serve her well as she tackles challenging problems and modulations expected from intense scientific research such as those proposed to tame and reset the immune system with JAK inhibitors in HIV infected persons."

In 2005, Howard Hughes Medical Institute launched the Med Into Grad Initiative to address the growing gap between basic biology and medicine and offered grants to enhance or initiate PhD programs that would provide students with a better understanding of medicine and pathobiology. The ACTSI was granted an HHMI Med Into Grad award to develop the Certificate Program in Translational Research and enhance the understanding of and an appreciation for medically relevant principles by future PhD biomedical researchers at Emory and our partner institutions.

“There is nothing clinical like this in the PhD program and that was one of the reasons I wanted to do the CPTR. The PhD program is very much slanted towards basic science. They want to shape you into an academic scientist and everything that can allow you to succeed in a laboratory environment, which is good, but it doesn’t allow you to see the other side if you desire to develop a drug or use academia as a foundation to do other things that can be more broad reaching,” said Gavegnano.

In fall 2010, RETCD launched the CPTR and to date, 16 PhD students and postdocs have completed the program, 11 are currently enrolled for a second year, and seven new students are beginning the program this fall. “The goal of the program is to help students bridge the gap between basic and clinical/translational research and gain a better appreciation of clinical/translational research and hopefully apply that knowledge in their future research careers,” said Tangpricha.

Gavegnano is currently a post-doc fellow in Schinazi’s lab testing the JAK inhibitor. “I’m personally using the understanding of what happens to a drug after preclinical. The translational process is something Dr. Schinazi is familiar with but I knew nothing. When you have a new drug I now know what you have to do to get it in the clinic. At first it was a class and now it is a reality,” she said. Day-to-day Gavegnano works to further the drug in vitro and in vivo through wet lab work, primate models (studies) at Yerkes Primate Research Center, data analysis, sharing her work through abstracts/publications, and writing grants to keep the ball rolling. She is immediately using what she learned in the CPTR in a real-life setting.

ACTSI does not stop with the CPTR. The partnership between Emory University, Morehouse School of Medicine, and Georgia Institute of Technology also sponsors the Kauffman FastTrac Tech Venture Course for entrepreneurs, the Capstone Design Course, the Academic & Industry Intersection Annual Conference, and a joint Georgia Research Alliance position identifying ACTSI-supported work ready to translate into a startup company. The ACTSI’s RETCD also offers a Master of Science in Clinical Research through Emory’s Laney Graduate School and MSM, including a KL2-Mentored Clinical and Translational Research Scholars Program and a TL1-Medical Scientist Training.

The ACTSI is a city-wide partnership between Emory University, Morehouse School of Medicine, and Georgia Institute of Technology and is one of a national consortium striving to improve the way biomedical research is conducted across the country. The consortium, funded through the National Center for Advancing Translational Sciences, part of the National Institutes of Health’s Clinical and Translational Science Awards, shares a common vision to translate laboratory discoveries into treatments for patients, engage communities in clinical research efforts, and train the next generation of clinical investigators.

Read more about a student’s path to industry using the CPTR