Grant Dorsey, MD, MPH, PhD

Professor In Residence

HIV, Infectious Disease, and Global Medicine, Infectious Diseases

Overview: Our malaria research group has been active for over 20 years, bringing together a diverse group of UCSF faculty members from the Departments of Medicine, Pediatrics, Clinical Pharmacology, Obstetrics, Gynecology & Reproductive Sciences, and Bioengineering & Therapeutic Sciences. Areas of interest include clinical trials for the treatment and prevention of malaria, antimalarial drug resistance, antimalarial drug discovery, pharmacokinetics and pharmacodynamics of antimalarial drugs, malaria in pregnancy, molecular epidemiology, sero-epidemiology, naturally acquired immunity to malaria, and public health surveillance. Laboratory work is performed at a number of laboratories at SFGH. A majority of our fieldwork is conducted in Uganda with the Infectious Diseases Research Collaboration (http://idrc-uganda.org/) and collaborators from Makerere University. We have a large field site in Eastern Uganda that includes several study clinics, a data center, an insectary, and a research lab with capacity to culture parasites and perform basic immunology, histopathology, and molecular biology studies. We also have a health facility based network at 68 sites around the country. We also have research projects at other international sites including Burkina Faso, several countries in Southern Africa, and countries in Southeast Asia. We have active collaborations with several international and domestic institutions including the London School of Tropical Medicine and Hygiene, Liverpool School of Tropical Medicine, Radboud Institute for Health Sciences, Stanford University, University of Washington, University of Pennsylvania, Johns Hopkins School of Public Health, Harvard School of Public Health, and Brown University.
Training and capacity building is a major focus of our group. We have mentored many medical students, graduate students, residents, and post-doctoral fellows, many of whom have gone on to successful careers in malaria research at UCSF or other institutions including Southwestern Medical Center, Yale University, Stanford University, and the London School of Tropical Medicine and Hygiene. We place a strong emphasis on providing opportunities for fieldwork and partnering U.S. based trainees with scientist from malaria endemic countries. Many of our trainees have been awarded mentored research career development awards including NIH F31 grants for doctoral students and K series grants for post-doctoral and Infectious Diseases fellows.

Subcategories

1) Clinical trials. Our group has a long history of conducting clinical trials, including dozens of antimalarial drug efficacy studies and evaluations of antimalarial drugs for the prevention of malaria in children and pregnant women. Currently funded studies include a randomized controlled trail comparing different regimens for the prevention of malaria and improvement of birth outcomes in pregnant women, evaluating the impact of chemoprevention in young children and the development of antimalarial immunity, and a large cluster randomized trial comparing long lasting bednets with different formulations of insecticides. These trials offer the opportunity to work on all aspects of trial design, implementation, and analysis as well as the opportunity for secondary data analysis and complementary translational studies.

2) Drug mechanisms, resistance and pharmacology. At UCSF we are engaged in antimalarial drug discovery, characterization of mechanisms of action of novel antimalarial compounds, characterization of the genotypes and phenotypes of malaria parasites with varied sensitivity to established and novel antimalarials, and evaluation of the pharmacokinetics and pharmacodynamics of antimalarial drugs. Working with collaborating groups in Uganda and Burkina Faso, we are maintaining surveillance for markers of antimalarial drug resistance, characterizing in vitro antimalarial drug resistance, and performing translational studies to better understand the interplay of antimalarial activity, drug resistance, parasite fitness, and drug pharmacokinetics. These studies offer opportunities to work in a range of translational research areas, from basic research at UCSF to translational studies in Africa.

3) Molecular Epidemiology. The large and diverse genomes of malaria parasites provide a tool to track infections within hosts, through populations, and between regions over time. Our team builds laboratory and analytical tools to extract this information and applies them with innovative field studies to understand details of transmission epidemiology that are difficult or impossible to measure accurately with traditional methods. These studies allow us to provide actionable data for public health and answer fundamental questions regarding the transmission biology and epidemiology of malaria. Projects are located at numerous sites in Africa.

4) Immunology. Immunity to malaria is a complex phenotype, requiring integration of numerous streams of data including molecular and immunologic analysis of the parasite and host. We work on novel ways to more accurately measure various manifestations of clinical immunity and study the relationships between infection and various aspects of the host response including humoral immunity, cellular immunity, and comprehensive systems immunology projects. Novel ways of using antibodies for precisely determining prior exposure are also being evaluated for public health surveillance. Our group has also made significant progress in elucidating the immunopathogenesis of human malaria, including definition of regulatory and effector cell populations that are associated with immunity. Currently funded studies investigate how the natural acquisition of antimalarial immunity is altered by chemopreventive interventions, how immunogenetic factors influence susceptibility to malaria, and how fetal T cells respond to pathogen-derived antigens encountered in utero. These studies leverage large and well-characterized human biospecimen banks and provide numerous opportunities for add-on studies to investigate the host immune response to malaria and co-pathogens.

5) Epidemiology and Surveillance. Our group has pioneered longitudinal studies of malaria in cohorts living in settings with varying transmission intensity and population level control interventions. These studies have greatly improved our understanding of malaria epidemiology, clinical measures of immunity, and the impact of various environmental and vector control strategies. In addition, these studies have generated an immense bio-specimen repository and has been used complementary basic science and translational research project. Over the past 15 years we have also developed a health facility-based malaria surveillance network in collaboration with the Uganda Ministry of Health. This network currently collects individual level electronic data from all patients presenting to the outpatient departments at numerous sites around Uganda.

Education
2019 - Diversity, Equity, and Inclusion Champion Training, University of California
PhD, 2004 - Epidemiology, University of California Berkeley
Fellowship, 2002 - Infecious Diseases, University of California San Francisco
MPH, 1997 - Epidemiology, University of California Berkeley
Residency, 1996 - Internal Medicine, University of California San Francisco
MD, 1993 - Medicine, Southwestern Medical Center
BA, 1989 - Microbiology, University of Texas