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Blog: Students & Faculty Share How UNC Project-China is Changing the Scope of Research into Sexual Health
Joseph Tucker, MD, PhD, is the Director of UNC Project-China. Myron Cohen, MD, is the Director of UNC’s Institute for Global Health & Infectious Diseases. Dr. Cohen and his wife Gail Henderson, PhD, first began working in China in 1989. UNC researchers organize an annual training for Chinese researchers as well as American medical students. Below Drs. Tucker and Cohen reflect on how UNC Project-China has evolved, and students who attended this September’s South China-UNC STI Training Course & Research Workshop blog about how learning from top faculty in the US and UK is improving the field of sexual health treatment, STI prevention and research.
In 1989, UNC Professors Gail Henderson, PhD, and Myron (Mike) Cohen, MD, travelled through Guangzhou, in southern China near Hong Kong, en route to an infectious diseases collaborative US-China research project. At that point, there was no U.S. Embassy in China, and it was one of the very first US-China medical research programs.
Now, 26 years later, a UNC team is trailblazing collaborative infectious disease research projects in South China.
In 2010, the Institute for Global Health and Infectious Diseases (IGHID) recruited Joseph Tucker, MD, PhD, to form a center for excellence in China focused on sexual health research, teaching and service. This center is UNC Project-China.
The UNC Project-China pools talent and resources from three Chinese institutions: Guangdong Provincial Dermatology and STD Control Center, Guangzhou Eighth People’s Hospital and the Sun Yat-sen University. Chinese leaders include Dr. Bin Yang (Guangdong Provincial Center), Dr. Weiping Cai (Guangzhou Eighth People’s Hospital), and Dr. Yuantao Hao (Sun Yat-sen University).
This unique and important partnership led to the “UNC-South China Training Center” supported by a five-year grant from the U.S. National Institutes of Health (NIH) Fogarty International Center. This training center support was unusual because of the extent to which Chinese financial support was integrated into the overall strategy, setting the stage for a strong and sustainable collaborative partnership.
Every year since its inception, the UNC Project-China has grown. On Sept. 9th, three UNC Chapel Hill faculty, Professors Ronald Swanstrom, PhD; J. Victor Garcia, PhD; and Kevin Robertson, PhD, all took part in a day-long symposium focused on HIV cure research. This conference was the first of its kind in the region, drawing an audience of more than 100 individuals and many exuberant reviews.
This event has been followed by a series of workshops and one-on-one research mentoring sessions attended by UNC faculty including Cohen, Arlene Seña-Soberano, MD, MPH, and William Miller, MD, PhD, MPH. A select group of 24 junior STD/HIV investigators in the region had one-hour meetings with UNC training faculty in addition to a one-hour meeting with a UNC health sciences librarian, Jennifer Walker, MLS, and Mellanye Lackey, MSI. Trainees also had an opportunity to benefit from the mentorship of Kevin Fenton, MD, Director of Health and Wellbeing at Public Health England; Rosanna Peeling, PhD, Chair of Diagnostics Research at the London School of Hygiene and Tropical Medicine (LSHTM); David Mabey, MD, PhD, Professor at LSHTM; Chongyi Wei, DrPH, MA, Assistant Professor of Epidemiology at the University of California at San Francisco (UCSF); and many others.
The UNC Project-China now has six postdoctoral fellows, including Weiming Tang, PhD, and Songyuan Tang, PhD, who both studied public health at the University of California at Los Angeles (UCLA); Lai Sze Tso, PhD, who studied sociology at the University of Michigan; Haochu Li, PhD, and Ngai Sze Wong, PhD, who both studied public health at the Chinese University of Hong Kong; and Andrea Shahum, MD, PhD, who studied infectious diseases at UNC. Fogarty Fellows supported by the UJMT consortium include Weiming Tang, PhD, and Fengying Liu. The Program also hosts two U.S. medical students: Jessica Mao of UCLA and Yilu (Lulu) Qin of the Cleveland Clinic Lerner School of Medicine supported by fellowships from Fogarty-Fulbright and Doris Duke respectively.
The UNC Project-China has been remarkably successful. The trainees had a total of 14 abstracts at international conferences, 25 research manuscripts and two UJMT Fogarty Global Health Fellowships. In addition, our trainees had two original research studies accepted for presentation at the Lancet-Chinese Academy of Sciences Summit in Beijing. The UNC team also was commissioned to write seven distinct systematic reviews to inform three sets of World Health Organization (WHO) guidelines – HIV testing, antiretrovirals (ARV), and hepatitis testing guidelines. The Training Center has been extremely productive at the UNC center in Guangzhou with several regional research awards, a WHO commission and new research positions for trainees.
One unique focus is SESH – social entrepreneurship for sexual health. The SESH goal is to leverage entrepreneurial concepts, like crowdsourcing, to improve public health. The SESH (www.seshglobal.org) research team was selected by the WHO-TDR group as one of 25 global innovators as part of their Social Innovation in Health Initiative.
The UNC Project-China has grown rapidly, and is leading to strong, stable collaborations and activities important to China and global health. Now in the midst of our yearly meetings, we have asked three of our students to blog about our recent three-day training.
A volunteer opportunity as a college student at McGill University in Montreal, Canada, shifted the course of Thibaut Davy’s life. He was studying political science, but also contemplating a career as a doctor. To explore a career in medicine, he began spending several hours a week at a palliative care center for people living with HIV.
“I liked being able to spend four hours with the same person, which I realized was not an amount of time a doctor would be able to spend with someone,” says Davy, who has worked with UNC’s Center for AIDS Research (CFAR) Clinical Core Team for nearly two years and recently began a dual master’s of science degree in public health-doctorate in epidemiology program at UNC. “I also became sensitive to the stigma people living with HIV face. Many of the nursing students had to be reminded that they didn’t need to don gloves to give someone a hug. This really piqued my interest in a career in HIV.”
Davy’s experience at the palliative care center in Montreal also exposed him to the many faces of HIV – men who have sex with men, heterosexual women, African refugees and intravenous (IV) drug users. He learned through McGill’s internship office that he was eligible to spend the summer in between his second and third year of college working with the United Nation’s HIV/AIDS program in Panama. He applied and was accepted.
“USAID contracted with John Snow, Inc., to conduct a health needs assessment of transgender women in Central America and they needed to build a relationship with local people in each country as this population is largely underground,” says Davy, who was born in France and speaks French, Spanish and English. “I helped them conduct interviews in Spanish in Panama with about 20 transgender women.”
It was in Panama that Davy was first introduced to the field of epidemiology. He met an epidemiologist who was modeling research about HIV transmission.
“I really thought I might graduate and look for jobs that dealt with health policy since I was a political science major, or maybe I would work for an NGO (non-governmental organization),” Davy says. “I had never considered a career in research before.”
He returned to his final year of college at McGill and received an unexpected phone call from the university’s internship office. There was an opportunity to work in Kenya the summer after Davy graduated. Usually the university preferred undergraduates to take these positions so they could share their experiences once school resumed in the fall. However, they believed Davy would be the best fit for this opportunity. After graduating from McGill, he departed for Nairobi, Kenya, in June of 2013.
The program was originally created by the University of Liverpool in England and then transitioned to a Kenyan NGO. There were clinics for HIV testing and treatment as well as a research division, but they did not do any clinical trials. Davy was first assigned to the research division where he worked entering data, filing reports and auditing rape records kept by public hospitals. He was then introduced to the leader of the NGO’s LGBT division. Through this division, he had the opportunity to update a risk assessment form, research the best prevention techniques and develop an educational plan to target populations most at risk in Kenya for contracting HIV. Yet, when he left Nairobi in August 2013, it was unclear if his work was ever going to be implemented.
“I noticed vast differences immediately between the program I worked on in Panama the summer before and the one I worked on in Kenya,” Davy says. “The questions on the risk assessment form were very hetero-centric in Nairobi. I realized Kenya was not as accepting a society of the LGBT community as Panama.”
Davy returned to the US and his family’s home in Raleigh. There, he began applying for jobs in HIV policy, advocacy and research. He was hired to work for Sonia Napravnik, PhD. Napravnik holds dual appointments as an Assistant Research Professor in UNC’s Division of Infectious Diseases within the School of Medicine and the Department of Epidemiology within the Gillings School of Global Public Health. She oversees the UNC Center for AIDS Research (CFAR) HIV Clinical Cohort study, and has more than 15 years of experience in HIV clinical and epidemiological research with a focus on analytic methods using observational clinical data.
Davy began working with Napravnik in the fall of 2013, helping update the data of newly consented patients. He reads through a patient’s medical records from the date he or she was diagnosed with HIV and logs information such as lab results and history of any complications or illnesses. He also heads to the ID Clinic in the NC Memorial Hospital on UNC’s campus once a week to survey patients before they meet with their infectious diseases specialist to ensure the data on every patient is kept current in the system. Davy also assists with pulling information requested for data queries. The experience inspired him to apply to UNC in late 2014 for the dual master’s of science degree in public health and doctoral degree in epidemiology program through the Gillings School. Napravnik encouraged him to consider a career in epidemiology.
“Thibaut’s abilities to critically contribute across the research spectrum of our diverse HIV clinical research portfolio supported my decision to encourage him to pursue a career as an epidemiologist,” says Napravnik. “Thibaut has a natural aptitude for conducting thoughtful and rigorous research, which makes him an exceptional junior investigator. He also has a dedication and passion for HIV research that is contagious. He brings energy, insight and innovation to the work we do, qualities needed to solve the intractable problems of the global HIV epidemic.”
In addition to Napravnik, Davy also credits Joe Eron, MD, with helping him decide on continuing to work at UNC’s CFAR while he attends classes at UNC for his graduate and doctoral degrees. Eron is the Director of the UNC CFAR’s Clinical Core, a Professor of Medicine in the Division of Infectious Diseases and an Adjunct Professor in the Department of Epidemiology. Davy said Eron encouraged him to submit an abstract to the International AIDS Society meeting this summer, the annual gathering of infectious diseases researchers from around the world.
“Thibaut is a remarkably quick study. He has learned a tremendous amount about our work, and HIV observational research in general, in a very short period of time,” says Eron. “We need young, agile minds to continue HIV research, and Thibaut has the ability and the passion to become a leader in the next generation of HIV clinical scientists.”
When he finds any down time in between working for the CFAR and attending class, Davy enjoys playing the piano, listening to jazz music or reading historical fiction. He looks forward to his next few years of school and the career ahead, especially if given the opportunity to remain at UNC upon graduation.
“I would really like to remain in academia and HIV research, especially at UNC because I think the people here are brilliant,” Davy says. “Sonia and Joe are so supportive and really take mentoring seriously. And UNC is located in the South, which is the location in the US where the HIV epidemic continues. One question I would like to explore is why people living with HIV have higher incidences of cancer, heart disease and renal disease. There is little data to explain why this is the case. Is it biological? Is it due to the virus being in the body? Is it due to changes in the immune system? Or are people living with HIV more likely to engage in social behaviors that lead to heart disease and cancer, like smoking? It will be hard to untangle all of these factors, but I am excited to help with this challenge.”
A unique molecule developed at the University of North Carolina at Chapel Hill, Duke Medicine and MacroGenics, Inc., is able to bind HIV-infected cells to the immune system’s killer T cells. It could become a key part of a shock-and-kill strategy being developed in the hope of one day clearing HIV infection.
The molecule is a type of bi-specific antibody known as a Dual-Affinity Re-Targeting protein, or DART®. It was engineered by MacroGenics, using HIV-targeting antibodies discovered at Duke. Employed increasingly in cancer research, bi-specific molecules have shown effectiveness in helping the immune system recognize and clear tumor cells. In this case, pre-clinical models demonstrate that DART creates a fatal union between HIV-infected cells and killer T cells.
When Julia Sung, M.D., lead author and clinical assistant professor in medicine at UNC, used DART molecules in combination with additional agents that wake up latent reservoirs of the virus hiding in the body, the approach showed early promise as a way to clear HIV infection.
“This is an exciting approach that has the potential to clear a pool of cells that are so hard to get rid of — virus that lies silent and hidden in the host,” said Barton Haynes, M.D., director of the Duke Human Vaccine Institute and a senior author of a study describing the molecule in the Journal of Clinical Investigation (JCI).
“These drugs would be combined with other drugs that activate expression of HIV in the cells,” Haynes said. “As soon as they are awakened, the DART molecules hit them and causes the killer T cells to destroy the virus.”
Haynes and colleagues at UNC, the University of Alabama-Birmingham, and MacroGenics report in the Sept. 28 online edition of JCI that the DART strategy was highly effective in clearing HIV in laboratory experiments.
To try to model what might happen if patients were treated with DART molecules to clear persistent infection, lymphocytes were taken from patients on HIV therapy. These cells were then re-infected with different HIV virus subtypes, and with viruses previously recovered from the same patient’s latent viral reservoir. When the patient cells expressed these various viral strains, DART molecules facilitated CD8 “killer” T cell clearance of the infected cells.
In another pre-clinical modeling experiment in the laboratory, exposing HIV-positive patients’ cells to HIV latency reversing agents –- drugs which are under development to force dormant HIV out of hiding — the DART molecules showed potential to be effective immunotherapeutic weapons to clear these latent HIV reservoirs.
“A similar approach is being tested to cure some forms of cancer,” said David Margolis, M.D., co-corresponding author and professor of medicine, microbiology and immunology at UNC. “This idea is being repurposed for curing HIV with our partners at Duke and MacroGenics. This paper shows that DART molecules can recognize different strains of HIV, bind to cells, and clear and kill the virus in many different scenarios.”
“While the research into DART molecules is still in early stages, it is very exciting to see how these molecules can turn otherwise ineffective T cells into potent killing machines against HIV latently infected cells,” Margolis said.
The researchers said the DART approach is especially promising because the molecule recruits from a large pool of T cells, regardless of specificity, creating a broad attack that is not dependent on targeting any single HIV strain.
“Because we are targeting a region of the virus envelope that appears in all mutations of the virus, we think it will make it much easier to be broadly utilized — at least from our laboratory data,” said co-corresponding author Guido Ferrari, M.D., associate professor of surgery and molecular genetics and microbiology at Duke. “These DART molecules will facilitate the recognition. We are eager to see how this translates to human studies.”
“This is a great opportunity for MacroGenics to expand our DART platform for therapeutics applications beyond oncology and autoimmune disorders and into infectious diseases,” said Scott Koenig, M.D., Ph.D., president and CEO of MacroGenics. “We are encouraged by our proof-of-concept studies that show HIV DART molecules to be potent immunotherapeutic agents with the potential to reduce HIV reservoirs in patients.”
Study authors at UNC include Margolis and Sung, along with Carolina Garrido; Nancie Archin; Brigitte Allard; Jennifer Kirchherr; JoAnn D. Kuruc; Cynthia L. Gay; and Myron S. Cohen.
In addition to Haynes and Ferrari, study authors at Duke include Joy Pickeral; Sherry A. Stanfield-Oakley; Justin Pollara; Celia LaBranche; Mattia Bonsignori; M. Anthony Moody; Robert Parks; Kelly Soderberg; Hua-Xin Liao; and David Montefiori.
Authors at MacroGenics include Koenig and Liqin Liu; Chia-Ying Kao Lam; Yinhua Yang; Paul Moore; Syd Johnson; and Jeffrey L. Nordstrom. Author Christina Ochsenbauer is from UAB.
Haynes, Ferrari, Bonsignori, Moody and Liao have filed patent applications on the two monoclonal antibodies described and related antigens used in the study.
This study received funding from the National Institutes of Health to the Collaboratory of AIDS Researchers for Eradication (U19 AI096113); Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (UM1 AI10064); the UNC Center for AIDS Research (P30 AI50410); and the Duke Center for AIDS Research (P30 AI64518).
Full funding support and conflicts of interest are disclosed in the published study.
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IGHID and Office of Research Communications Directors Join School of Media and Journalism’s New Class
If a room is filled with a collection of newspaper, radio and television reporters as well as UNC’s public relations professionals, you know either something very good or very bad is about to be announced. Luckily, the news coming out of UNC’s School of Journalism and Mass Communication on Friday, Aug. 21, was nothing, but good – fantastic even.
Widely known by its nickname, the J School is shedding its former title and will now be called the UNC School of Media and Journalism. It is also adopting a new motto and revamping a class launched in the spring based on student feedback. After landing the top spot against other schools around the country in the Hearst Broadcast Championships last year for the second time in three years, Dean Susan King and her team decided “Start Here, Never Stop” was an accurate tagline for how they hope their graduates will leave Carolina, but never stop the award-winning pursuit of accurate, ethical and well-rounded news coverage. And a class launched last semester by Charlie Tuggle, PhD, Senior Associate Dean for Undergraduate Studies, expanded this semester to include not only print and broadcast personnel to serve as mentors for students enrolled in the News Bureau class, but also include UNC public relations partners and a new name – Media Hub.
“In our school, we try to speak to the realities of a rapidly changing media landscape,” says Tuggle. “Our name change to the School of Media and Journalism reflects that as does our commitment to having students work together across platforms so we can prepare them for jobs in the media fields. The idea of Media Hub came out of our long-range strategic plan. We initially called the class News Bureau, but the feedback we got was that the name was a bit restricting for those studying PR and marketing. We have a definite role for such students in the class, so we changed the name to Media Hub to reflect the idea that it’s a collaborative, high-level exercise in not only finding and producing stories of state-wide importance, but also marketing those stories to professional media partners across NC.”
Those partners include reporters and news directors from WUNC, WRAL, WECT, the News & Observer, the Daily Tarheel, Duke University and UNC public relations and marketing professionals including IGHID Communications Director Morag MacLachlan and UNC’s Office of Research Communications Director Layla Higgins Dowdy. MacLachlan got her start as a television reporter for a CBS-affiliate in Maine, where she won a Maine Association of Broadcasters Award and a Radio & Television News Directors Association (RTNDA) fellowship to report for a summer in Germany and Belgium with the Radio in the American Sector (RIAS) Kommission. She then switched to newspaper reporting and won the New England Press Association’s first place award for health reporting in 2006 for a story about water pipes in a local town lined with a carcinogen. She then worked in clinical and research communications for both internal and external audiences at Beth Israel Deaconess Medical Center and Brigham & Women’s Hospital in Boston before taking the job with UNC IGHID in December.
Dowdy, holds two master’s degrees- one in integrated marketing and one in business administration. She spent years working for NASA, holding positions including public affairs specialist, information and communications coordinator, strategic communications specialist, and communications and outreach specialist. She has served as the Director of UNC’s Office of Research Communications for more than a year.
“One of the most highly visible research stories to come out of UNC over the past few months did not originate from any official source,” says Dowdy. “A student-created video of Jeff Powell’s 3D printed arm went viral and touched millions. Partnering with Media Hub gives me the ability to tap into the unique voice of the students, and their knowledge of the amazing things their peers are working on at UNC. My hope is that by working with me, the students will be exposed to even more of the incredible research endeavors at the University, and will be able to help us develop new, creative ways to communicate the impact that research at UNC has on North Carolina and the world.”
Student Nat Zhai recently wrote a story about vaccinations and says the access to people in the field of journalism as well as the experts the public relations teams on campus can connect her with to enhance her own reporting skills has her excited about the semester in Media Hub.
“I participated in Media Hub because I wanted an opportunity to produce stories on topics that I am deeply passionate about – the environment, energy and human rights,” says Zhai, who is studying at UNC from Malaysia. “I hope that I will be able to learn how to find stories, investigate leads and publish my stories in this class. Working with on and off-campus partners is also a valuable experience as we get to interact with people and know what information is out there and what people want to read.”
Arlene Seña, MD, MPH, sits at her desk at the Durham County Public Health Department gearing up for a meeting with some of the staff she manages there in her role as Medical and Laboratory Director. The modern building at 414 East Main Street in Durham is designed to prevent anyone walking in for community health or human services from leaving without being properly linked to resources and materials in their native language.
“I really care about the needs of uninsured, vulnerable populations,” Seña says. “I find this work truly rewarding.”
Seña, who is from the Philippines but grew up in North Carolina, not only believes in every individual having access to the services they need to live safe and healthy lives, but she is also leading research studies and training infectious diseases fellows who share her passion for community health in her roles as an investigator and Associate Professor of Medicine at UNC’s Division of Infectious Diseases. UNC is also her alma mater for not just her medical degree, but also her master’s in public health.
“Arlene is a passionate researcher and clinician,” says Christopher Hurt, MD, Clinical Assistant Professor at UNC’s School of Medicine and a clinician-scientist in UNC’s Division of Infectious Diseases.
Seña applied for and received funding from the U.S. Centers for Disease Control and Prevention (CDC) to lead a project at the Durham County Public Health Department that explored whether a community health setting could bring public health professionals together and provide the community, especially uninsured, vulnerable populations, with access to testing and treatment for hepatitis C virus (HCV). She enlisted the assistance of Hurt and their fellow UNC infectious diseases colleague David Wohl, MD, Associate Professor of Medicine, and leader of the North Carolina AIDS Training & Education Center (ATEC). And although a graduate and an employee of Carolina, Seña reached out to rival Duke by asking Andrew Muir, MD, Chief of Gastroenterology, to join her research team, as HCV is also his clinical and research interest.
“I wanted to assemble a team from UNC and Duke that could all be accessible partners to us in Durham,” Seña says. “Andrew Muir has been a key supporter of our project to provide HCV services to the uninsured of the community. We are all advocates for community health as well as testing, diagnosing and treating vulnerable populations living with hepatitis C virus.”
From December 2012 – March 2015, nearly 3,000 HCV tests were conducted among people from a variety of at-risk populations including past or current intravenous drug users, the homeless, the incarcerated, and Baby Boomers who came into the Durham County Public Health Department. Of those who were tested, 17 percent or 510 people tested positive for HCV antibody. Of those 510, more than half or 386, had detectable viral load in their blood for HCV, meaning they were at-risk of not only infecting someone else, but of having the untreated infection harm their liver. The majority of the 3,000 people screened who tested positive for HCV were African American men who were part of the Baby Boomer generation of persons born between 1945-1965. This meant that older, minority men were the most at-risk among these vulnerable populations for chronic HCV infection and for the potential consequences of cirrhosis and liver cancer.
“Christopher, Andrew and myself agreed to see HCV-infected patients without getting paid for it in Durham,” Wohl says. “We then saw roughly 200 patients who we had tested positive for HCV at the Durham County Public Health Department for an initial assessment and counseling. Then Christopher and I saw some of these patients in UNC’s ID Clinic in the NC Memorial Hospital on campus and Andrew saw patients at Duke for HCV treatment options.”
Seña’s study proved her hypothesis that HCV testing and linkage to care can be facilitated at the local public health level by leveraging existing programs and engaging a team of public health providers. Her project “Expanded Testing for Hepatitis C Virus Infection in a Public Health Department and Linkage to Care in Durham, North Carolina” was presented at the 2015 National Summit on HCV and HIV Diagnosis, Prevention and Access to Care, and will be published later this year in the journal Public Health Reports.
But the work is far from over. The tricky part now is that there is a cure for HCV, but unfortunately people living with HCV have to be really sick, nearing liver cirrhosis, to get this treatment paid for by insurance. Seña, Hurt, Wohl, and Muir are working on keeping those who tested positive for HCV, but who are not sick enough yet by the insurance standards, linked to care as they fight to get them treatment before their health takes a dangerous and far more expensive turn.
“HCV causes inflammation in the body, which causes scar tissue and prevents the liver from working normally,” Seña says. “We don’t want people who test positive for HCV to have to wait until this scar tissue begins, progresses to fibrosis and eventually to liver failure before they can receive the newer drugs. We have interferon-free regimens for people living with HCV that will cure this infection and not cause debilitating side effects, but we have limited access to these expensive drugs and only a few specialists have training in HCV management. This is frustrating from a clinical standpoint because although more patients may know they have chronic HCV infection, we can’t easily get treatment for mostly uninsured persons until they are far more ill. We need to focus our public health efforts not only on HCV testing, but also on increasing access to HCV care through linkage services and increased provider education.”