Not everyone can point to a single experience that shaped the course of his or her career.
Dr. Thomas Uldrick, the former clinical director of the National Cancer Institute’s HIV & AIDS Malignancy Branch who was named deputy program head of Global Oncology at Fred Hutchinson Cancer Research Center in December, can name two.
The first came before he was even in medical school. Growing up the son of an engineer and a science teacher in Silicon Valley, Uldrick had excelled in high school math. Rather than following his dad into engineering as expected, he zagged, and opted for Latin American Studies at the University of California, Berkeley. A move to New York City and a year of soul-searching led to signing up for pre-med classes at Columbia University — and a fateful job at Gay Men’s Health Crisis, the world’s first and most iconic provider of HIV/AIDS prevention, care and advocacy services.
The job was helping HIV patients in clinical trials stick to a complicated experimental therapy that involved taking multiple drugs throughout the day and night. It was 1994, and on a personal level, working with young men who had gone blind or suffered other disabilities from AIDS-related infections affected Uldrick deeply.
On a professional level, the experience ignited a passion for clinical research.
The clinical trials in question were of the Lazarus-like antiretroviral drug cocktails that would transform AIDS from a death sentence to a manageable chronic disease.
“My interest in HIV-associated cancers grew out of the HIV work I was doing in my pre-med training,” said Uldrick, in a recent interview in his still-spare office on the Hutch campus. “I saw how science could change an epidemic.”
The experience sparked what would become an abiding interest in HIV and the immune system. After medical school, Uldrick gravitated toward HIV-associated cancers during his residency and postdoctoral clinical training in hematology and medical oncology at New York Presbyterian/ Columbia University Medical Center.
Cancer was part of HIV/AIDS from the epidemic’s beginning. In the earliest days, non-Hodgkin lymphoma, the once-rare Kaposi sarcoma and, in women, cervical cancer became known as AIDS-defining cancers. They signaled that a person’s HIV infection had progressed to full-blown AIDS.
Since the advent of antiretroviral therapy for HIV in 1996, full-blown AIDS and AIDS deaths have dropped dramatically. But the association between HIV and cancer remains. Even on antiviral treatment, HIV patients are at higher risk of developing cancer, not just the traditional AIDS-defining cancers but across the board. Among the 37 million people around the world living with HIV, cancer is now a leading cause of suffering and death.
In New York, the HIV-related cancers Uldrick saw were mostly lymphomas. In a postdoctoral fellowship in Durban, South Africa, in 2008 — shortly after antiretroviral therapy became available there — he saw lymphomas and more, including Kaposi sarcoma, a cancer caused by infection with a herpes virus now known as Kaposi sarcoma herpesvirus, or KSHV. The virus leads to cancer mostly in people who also have a weakened immune system, thus its association with HIV/AIDS.
Uldrick spent three months helping Dr. Anisa Mosam of University of KwaZulu-Natal analyze data from a clinical trial she had done on an experimental Kaposi treatment, but the experience resonated much longer. Over the years, he maintained that and other relationships he made in South Africa, collaborating on research papers and advising students on their master’s theses.
“In South Africa, where the HIV epidemic is worse than any place else in the world and the majority of lymphomas were HIV-associated, I became acutely aware of the need for really innovative, high-impact research in this area,” he said of this second career-defining experience. “I felt that my research interest could potentially have a very big impact if I focused on international projects.”
Uldrick returned from Durban to lay the groundwork for a research collaboration between Columbia and KwaZulu-Natal universities that continues today. (Around the same time — beginning in 2004 and formalized in 2008 — Fred Hutch was establishing its own Global Oncology program in Kampala, Uganda, partnering with the Uganda Cancer Institute.) Then the National Cancer Institute lured Uldrick away with a job offer that allowed him to hone his skills as a clinical investigator, designing and running novel clinical trials in HIV-associated malignancies as well as natural history studies evaluating the pathogenesis of KSHV-associated diseases. He worked under mentor Dr. Robert Yarchoan, who did some of the earliest HIV antiretroviral therapy trials at the NCI, then moved on to Kaposi sarcoma.
Uldrick spent the next 10 years at the NCI, rising to clinical director of the HIV & AIDS Malignancy Branch. Witnessing the advent of new immunotherapies that were beginning to transform cancer treatment, he became principal investigator for an ongoing, multi-center study — developed with immunotherapy researcher Dr. Martin “Mac” Cheever, who leads the NCI-funded, Fred Hutch-based Cancer Immunotherapy Trials Network — on a category of immunotherapies called checkpoint inhibitors in people with HIV and cancer.
In November, he presented early results from the study: The treatment, pembrolizumab (Keytruda), appears safe to use in patients with both advanced malignancies and HIV. Safety concerns had excluded this population from earlier trials of such therapies. This finding was a key first step in finding new treatments for them.
Recruited to join Fred Hutch Global Oncology, Uldrick was enthralled by the chance to continue his exploration of immunotherapy in Kaposi sarcoma and other HIV-related cancers in a part of the world where the burden is the greatest — as is the chance to make an impact.
“I was at a point in my career where I was hoping to focus more of my effort on high-impact global oncology research,” he said. “Fred Hutch is a leader in that.”
Uldrick’s goals matched those of Dr. Edus H. “Hootie” Warren, who last summer became head of Fred Hutch Global Oncology. A pioneering immunotherapy researcher, Warren aims to adapt what scientists in high-income countries are learning about the immune system into cost-effective therapies that can improve care a half a world away.
Shortly after accepting his new position, Uldrick made a first, quick visit to Kampala, where in 2015 Fred Hutch opened the state-of-the-art UCI-Fred Hutch Cancer Centre to house outpatient clinics, research laboratories and training facilities.
“I was really impressed by what’s been put in place there — the labs, the infrastructure for clinical trials, the clinics, the staff, the partnership with the UCI,” he said.
The Fred Hutch-UCI partnership started out treating and studying Kaposi sarcoma and childhood Burkitt lymphoma. Today, an ongoing study is underway that will increase the number of women screened for cervical cancer. In addition, the partnership is on the verge of launching its first treatment clinical trial — on breast cancer — this spring after months of preparation. Co-led by Fred Hutch oncologist Dr. Manoj Menon and UCI director and oncologist Dr. Jackson Orem, the trial will assess the feasibility of using all oral (rather than intravenous) chemotherapy drugs. It also will test an alternative diagnostic tool and use genetic sequencing to better define the molecular profile of breast cancer in sub-Saharan Africa.
When Uldrick made his first official visit to Kampala as deputy program head in January, he met with the regulatory staff at both the UCI and the Ugandan government to begin laying the groundwork for additional clinical trials, including ones looking at immunotherapy for HIV-associated lymphomas and Kaposi sarcoma.
Uldrick shares Warren’s goal to accelerate translating cancer treatment advances into innovations and approaches that work in low-resource settings. He is also quick to point out that the potential benefits of such research go both ways.
Take Kaposi sarcoma, which is one of the leading cancer killers in East Africa but rare in the United States. Rare, however, does not mean no one here is affected. Uldrick knows this firsthand, having run an NCI clinic that treated U.S. patients.
“In treating Kaposi sarcoma for a decade, I’ve seen many, many patients for whom existing therapies are not satisfactory,” he said. “If we can better understand the natural history of this disease and find ways to manage it more effectively by studying it more quickly in places where it’s common, that would have benefit for people in the U.S. for whom the disease is rare.”
Working in Uganda, which has high rates of all kinds of infections, also is an opportunity for Hutch researchers to hone their expertise in pathogen-associated malignancies and in the microbiome, Uldrick said. Researching cancer biology in different populations can both yield important findings for the basic science community and lead to the development of new treatments and diagnostics.
It also is a step toward addressing healthcare disparities, globally but also locally.
“In any country in the world, there are cancer disparities — certainly in the U.S., between South and North, African Americans and whites, urban and rural,” Uldrick said. “Understanding how to treat cancers in low-resource settings both effectively and cost-effectively could have benefits in the U.S. Anyone who wants to address cancer disparities has to address cancer research disparities. We are proud that we’re doing that.”
Mary Engel is a former staff writer at Fred Hutchinson Cancer Research Center. Previously, she covered medicine and health policy for the Los Angeles Times, where she was part of a team that won a Pulitzer Prize for Public Service. She was also a fellow at the Knight Science Journalism Program at MIT. Follow her on Twitter @Engel140.