For the 2019 Global Health Disparities Research Fellowship, you may apply to no more than two (2) of the research projects described below. Please read the descriptions carefully and ensure that you have the qualifications required to complete the project. If you have any questions, please contact the MHIRT program. Please DO NOT contact the professors directly.
CHINA I – HIV Transcription Activation and Latency Reversal (2 slots)
Title: Functional characterization of novel Tat partners key for activation of HIV-1 transcription and exit from latency.
Background: We are interested in elucidating the mechanisms and identifying the host cellular co-factors that control HIV-1 transcription and latency. It was 20 years ago when the human transcription elongation factor P-TEFb was first identified as a host cofactor for activation of HIV-1 transcription by the viral encoded Tat protein. Recruited by Tat to the viral LTR, P-TEFb stimulates RNA polymerase II elongation, a process essential for viral replication. Since 1997, this landmark discovery has provided the basic framework for our understanding of Tat function during the HIV life cycle, and P-TEFb remains the only widely accepted functional Tat partner till this day. However, published data suggest that Tat-transactivation involves more than the interaction between Tat and P-TEFb. A major effort of ours is thus aimed at identifying additional cellular factors that may associate with Tat-P-TEFb to further enhance Tat-transactivation.
Project Description: Recently, our laboratory has successfully identified the first new Tat partners since 1997. These partner proteins join P-TEFb to form a multisubunit complex called the Super Elongation Complex (SEC). The MHIRT research apprentice will use a combination of molecular and biochemical techniques to characterize this complex and determine the mechanism by which it cooperates with Tat to stimulate HIV-1 transcription and exist from latency. A portion of this project will be conducted over the summer in our collaborator’s lab, led by Dr. Yuhua Xue, at Xiamen University in China.
International Site: The partner for this project is Dr. Yuhua Xue in the School of Pharmaceutical Sciences at Xiamen University, China. Xiamen University has standard training and educational programs in place for international students at both the undergraduate and graduate levels. The visiting student will first be paired with a senior graduate student or a postdoc in the lab in order to become familiar with the daily operations in the lab. Once becoming more experienced, the student will be assigned an independent research project.
Required Qualifications: Advanced undergraduates or graduate students in MCB or other biology departments will have the appropriate background to complete this project.
CHINA II– Data Science for Advancing an Environmental Understanding of Infectious Disease Dynamics(2 slots)
Justin Remais (UC Berkeley) & Changhong Yang (China Centers for Disease Control and Prevention)
Title: Methods for optimizing the surveillance of infectious diseases in rapidly changing low- and middle-income environments
Background: This project — part of a recently funded NIH R01 — aims to develop statistical and computational approaches for better designing surveillance systems for high-priority global infectious diseases. Graduate or undergraduate students contributing to this project will advance methods to characterize dynamics of key infections in China in the presence of epidemiological and environmental changes, and subject to diverse surveillance system designs.
Project Description: Members of our team will be embedded in the Institute for Public Health Informatics at the China Centers for Disease Control and Prevention, where they will query and analyze high dimensional surveillance data streams on the dynamics of TB, malaria, dengue, schistosomiasis, Japanese encephalitis and leptospirosis. Graduate or undergraduate students contributing to this project will investigate the informational value of diverse surveillance architectures for monitoring these infections in China, and will acquire and analyze ‘Big’ surveillance data drawn from China’s massive NIDR system in order to do so. Other activities include the development of tools for the characterization and infectious disease surveillance networks using both epidemiological analysis and simulation science. Undergraduate, Master’s thesis and doctoral-level research opportunities are available within the group.
International Site: These studies are being carried out in collaboration with the Institute for Public Health Informatics at the China Centers for Disease Control and Prevention in Chengdu, Sichuan Province, PRC. The interns will be supervised by Dr. Changhong Yang, the director of the institute, as well as by Professor Remais and his scientific staff.
Required Qualifications: Undergraduate or graduate training in quantitative science is desirable, such as mathematics, modeling and simulation, computer science, environmental science, dynamical systems, engineering, population biology, or infectious disease epidemiology, although successful group members in the Remais Lab also have had backgrounds in physics, biology, anthropology and medicine. Technical skillsets, such as statistical analysis, geospatial analysis/GIS, time-series, differential equations, programming in any language (we are known to use R, Python, Matlab, Ruby, Perl, C, etc.), environmental modeling, theoretical ecology, or remote sensing, would be additionally desirable; effective written and verbal communication are essential.
INDIA I — Public Health Research Institute of India (PHRII) (2 slots)
Title: Molecular and Field Epidemiology Studies with Woman and Child Cohorts in Mysore, India
International Site Information: Public Health Research Institute of India (PHRII) is a Charitable Trust focused on public health research and evidence based care for women and children in India. Located in Mysore, the second largest city in Karnataka, PHRII has established collaborations with University of California, Berkeley; JSS University, National Rural Health Mission (NRHM); Karnataka State AIDS Control Society, and the Positive Women’s network. The organization has a full service diagnostic laboratory, a reproductive health clinic in central Mysore City, and mobile clinics serving rural areas of Mysore District.
Currently, some of the ongoing projects at PHRII include:
- Mental health issues in pregnant and postnatal women;
- Prevention of vertical transmission of HIV;
- Under 5-child mortality among disadvantaged populations in remote tribal and rural areas;
- Cognitive and mental development of infant and relationship to maternal mental health;
- Primary and secondary prevention of cervical cancer;
- Development of diagnostics for cancer screening and gestational diabetes;
- Understanding risk behaviors among emerging adults;
PHRII’s research collaboration with UCB Riley Laboratories has focused on the pathogenesis of infectious and chronic diseases; molecular epidemiology on tuberculosis and drug-resistant gram-negative bacterial infections; field epidemiology and slum health. For further information on the types of projects available through PHRII, you can go to the PHRII website.
Project Description: Candidates may select from a variety of ongoing projects in the areas described above including field based and/or laboratory work at PHRII in Mysore, India. Specific project selection will occur following the selection process and upon mutual agreement of the PIs and candidate. Interested applicants may seek additional information about available projects via Dr. Madhivanan who can be reached via the MHIRT office.
Required Qualifications: Preference will be given to candidates who have analytical skills, molecular microbiology or field experience and have worked in international settings before.
Title: Reducing AIDS stigma among health professionals in South India (The DriSti Study)
Project Description: This study brings together researchers from the University of California, San Francisco; Research Triangle Institute in Washington DC; St. John’s National Academy of Health Sciences in Bangalore, India; and the All India Institute of Medical Sciences in New Delhi, India to evaluate the efficacy of a promising intervention designed to reduce HIV stigma among Indian health professionals. The intervention builds on results of our previous research, identifying prevalence and drivers of stigma and discrimination in Indian healthcare settings among PLHIV, health care providers and uninfected patients.
Specifically, the study will:
1. Adapt our pilot-tested 3-session stigma reduction intervention for partial tablet-based delivery to increase its long-term sustainability in health care settings. The two tablet-administered sessions of the intervention use interactive touch screen methodology and video vignettes tailored to situations likely to be encountered by Indian nurses and ward attendants. The third session focuses on skills-building in a group format and is co-facilitated by a PLHIV.
2. Evaluate the efficacy of the intervention in 24 hospitals in North and South India on:
a) behavioral manifestations of HIV stigma, including endorsement of coercive policies, behavioral intentions to discriminate, and non/stigmatizing provider-patient interactions.
b) the factors underlying stigma proposed by our conceptual model and targeted in the intervention modules, including fears and misconceptions regarding casual transmission (instrumental stigma), and negative attitudes toward marginalized, vulnerable groups (symbolic stigma).
Across the globe, HIV stigma inflicts hardship and suffering on people with HIV and has been found to reduce the likelihood of seeking HIV counseling and testing and PMTCT. Stigma also deters infected individuals from disclosing their status, seeking timely medical treatment for HIV-related problems, reduces ART adherence, and leads to delays in clinic appointments and prescription refills, which can lead to virologic failure and the development and transmission of drug resistance.
Medical professionals unfortunately constitute a significant source of stigma for PLHIV. The study will yield valuable information on the efficacy of the intervention strategies in reducing stigma and improving patient-interaction skills among ward staff and nursing students. We expect this knowledge will inform the development and implementation of future AIDS stigma reduction programs efforts in India and similar settings.
Research site: St. John’s National Academy of Health Sciences (SJNAHS), Bangalore.
INDIA III – Validating a Low-cost Treatment Adherence Monitoring Device
Title: Tel-Me-Box: Validating and testing a novel, low cost, real-time monitoring device with hair level analysis among adherence-challenged patients
Project Description: “Tel-Me-Box” is a small, low-cost, adherence monitoring device, developed by our team that transmits a wireless signal to a server when opened. Since it cannot assess actual drug ingestion, validation against a biological measure of adherence is crucial. The overarching hypothesis of this application is that adherence data captured by Tel-Me-Box will demonstrate strong relationships with an objective biomarker of adherence (i.e. hair concentrations of ARVs) and predict virologic suppression in treated HIV-infected individuals. We additionally hypothesize that tailored real-time adherence feedback via this device will improve adherence rates to HIV therapy for adherence-challenged patients in a pilot randomized clinical trial. This five-year study is being conducted in collaboration with our colleagues at St. John’s National Academy of Health Sciences in Bangalore and the Karnataka State government.
Specific objectives include:
Aim 1 will refine Tel-Me-Box by adding tailored reminder features. We will also demonstrate feasibility of hair analysis in RLS by training local staff to conduct the relevant hair assays.
Aim 2 will validate the Tel-Me-Box adherence measure, using ARV hair concentrations and HIV viral load, and examine the predictive utility of Tel-Me-Box monitoring and hair drug levels on virologic suppression in HIV-infected patients.
Aim 3, will conduct a pilot RCT to examine acceptability and feasibility and estimate the effect size of automated tailored real-time adherence reminders on hair ARV concentrations, device-monitored adherence, and viral load suppression in adherence-challenged patients.
Novel, validated methods to monitor adherence to HIV treatment in real time are urgently needed given the well-known limitations of self-reported adherence, pill counts, and medication electronic monitoring system caps. In order to be scalable and sustainable in LMICs, such devices need to be low-cost and designed in a way that does not increase the risk of accidental HIV disclosure and subsequent stigma. Devices which both monitor adherence in real time and provide tailored reminders to patients for medication-taking have the potential to greatly improve adherence to HIV treatment as well as to treatment for other chronic diseases.
Research site: St. John’s National Academy of Health Sciences (SJNAHS), Bangalore.
Title: From asymptomatic parasitemia to cerebral malaria – investigating causes for a wide spectrum of malaria infection outcomes
Background: Our group has performed clinical, epidemiologic and translational research on malaria infection in Blantyre, Malawi for the past 30 years. The collaboration is between Michigan State University (MSU), Queen Elizabeth Central Hospital and the University of Malawi College of Medicine, with collaborative efforts based at several other US and UK based institutes. Our focus has historically been on severe disease with a long standing observational study on children with cerebral malaria being the ‘backbone’ of our research efforts. Recent efforts have moved away from the hospitalized patient and into the community where we are investigating the role of asymptomatic malaria infection and its role in maintaining a disease transmission reservoir.
Project Description: Topics of investigation may range from clinical to epidemiologic to basic science aspects of malaria infection and its consequences. We are specifically interested in the host and/or parasite factors that lead to varied clinical outcomes after Plasmodium infection. Techniques could range from immunologic to entomologic to molecular and genetic.
International Site: The project will be based in Blantyre, Malawi at the University of Malawi College of Medicine campus. Infrastructure in Blantyre includes a Pediatric Research ward for inpatient care, a Molecular and Genomics Core laboratory, a fully functional insectary, and several well-characterized rural sites within a 60km radius.
Required Qualifications: Students currently studying biology or public health are preferred.
NICARAGUA – Zika in Nicaragua (2 slots)
Title: Zika Virus Infection in Nicaragua
Background: In 2015/16, Zika virus (ZIKV) of the Flavivirus genus caused explosive epidemics that began in Brazil and spread throughout the Americas. Zika rapidly became a global concern, as it has been linked to severe congenital birth defects, including microcephaly and mis¬carriage, prompting the WHO to declare the Zika pandemic a Public Health Emergency of International Concern in February of 2016. As of February 15, 2018, 86 countries/territories had reported mosquito-borne ZIKV transmission, with 49 in the Americas. Over 2,500 cases have been reported in the US and its territories, with confirmed cases of sexual transmission. Many affected countries have reported increased numbers of congenital birth defects and Guillain-Barré syndrome (GBS) cases. Acute ZIKV infection is associated with inapparent or mild symptoms, ranging from myalgia, arthralgia, low-grade fever, conjunctivitis, maculopapular rash, and headache, to prostration. Much remains to be learned about the long-term sequelae of in utero or direct ZIKV infection in children, pathogenic mechanisms, and anti-ZIKV immune responses. No effective ZIKV antivirals or vaccines currently exist. Nicaragua reported its first Zika case in January of 2016. Since then, Dr. Eva Harris and long-term collaborators at the Ministry of Health and Sustainable Sciences Institute in Managua, Nicaragua, have been conducting a series of investigations of ZIKV infection and disease in a pediatric cohort study, a pediatric hospital-based study, a household transmission study, and three studies of Zika in pregnant women and their infants. The team also continues to study the related dengue flavivirus and the immunological interactions between ZIKV and dengue virus. Numerous virological, molecular biological, and immunological studies are ongoing.
Project Description: We aim to study the long-term immune responses to dengue and Zika viruses and the interaction between the two. The samples analyzed are captured at the annual sample collection as part of an ongoing community-based pediatric cohort study. The project includes determining previous ZIKV infection via enzyme linked immunosorbent assay (ELISA) and other methods. Regarding the studies of Zika in pregnant women and their babies, the children need to be followed for potential ocular, auditory, developmental and neurological sequelae and their samples need to be analyzed for anti-ZIKV antibodies.
International Site: Our foreign research site is embedded within the Ministry of Health of Nicaragua and administered in collaboration with the Sustainable Sciences Institute (SSI). Placement is available at the National Virology Laboratory of the National Center for Diagnosis and Reference (CNDR) of the Ministry of Health. The site is well-established, with over 100 study employees, and serves several large prospective studies of dengue, chikungunya, influenza and Zika. Numerous MHIRT, MPH, and PhD students have been hosted by SSI and the National Virology Laboratory in Managua. Dr. Harris has been collaborating productively with the Nicaraguan CNDR/Ministry of Health for over 30 years.
Required qualifications: Motivated undergraduate or graduate students with Spanish language proficiency. Previous laboratory experience, particularly molecular biology, required. STATA/SAS experience preferred, but not required.
Niger – Family Planning and Women’s Empowerment Research (1 slot)
Title: Room to Grow — improving women’s empowerment, gender equity, access to FP, and nutrition in women-led gardens in rural Niger
Background: The OASIS Initiative, a project of University of California, Berkeley and Venture Strategies for Health and Development, is helping catalyze a demographic transition in the Sahel region of Africa. In partnership with Population Services International and the Gates Foundation, OASIS has been working to address a complex set of challenges in the region, which includes rapid population growth, low contraceptive prevalence and low female empowerment. The Room to Grow study is testing an integrated solution that brings together community-based delivery of contraceptive methods and improved nutrition practices using a gender-synchronous approach within women-led gardens in the Zinder region of Niger. The project team hypothesizes that the integrated approach with women, girls, and their male partners will contribute to measurable improvements in the following outcomes: 1) women’s participation in household decision-making; 2) contraceptive use; and 3) dietary diversity. The combined increase in these primary outcomes will determine whether community gardens are an appropriate venue for reaching women with family planning and nutrition messages and if the gardens are a sustainable channel to deliver these messages. The study’s conclusions will be applied to inform the development of similar initiatives with the aim of achieving impact at scale.
Project Description: The student will work with the OASIS Niger’s research team in Niamey from June through August 2019 to finalize the study report, create a presentation with key findings (in English and French) and draft an article for publication.
International Site: The project is based out of the OASIS Initiative office in Niamey, Niger.
Required Qualifications: Motivated student with French language fluency. Student currently studying public health preferred, with a background in data analysis and strong written communication skills.
UGANDA – Translational Research in Malaria (1 slot)
Title: Susceptibility of Ugandan malaria parasites to available drugs and experimental compounds
Background: Our group performs translational and clinical research on malaria and other infectious diseases in Africa, at UCSF, and at Dominican University of California. The team at includes many additional faculty at UCSF and Makerere University, Uganda, studying different aspects of malaria.
Project Description: Malaria continues to be a tremendous health burden, particularly in Africa. We are interested in drug susceptibility and resistance, including molecular mechanisms of resistance, in the malaria parasite Plasmodium falciparum. We study parasites freshly isolated from Ugandan patients to assess sensitivity to a panel of standard antimalarials and compounds now in development as new drugs for malaria that are available from collaborators. When varied sensitivity is seen, as has been the case with a number of compounds, molecular studies assess potential mechanisms of resistance. Other ongoing projects within our group, all translational studies utilizing clinical data and samples from Uganda, include studies of malaria clinical and molecular epidemiology, antimalarial immune responses, malaria diagnostics, and impacts of parasite and host genetic polymorphisms on malaria transmission to mosquitoes.
International Site: Our studies are based in Uganda, with related laboratory studies at UCSF and Dominican University. Clinical and epidemiology studies are conducted at many sites in Uganda. Laboratory studies in Uganda are conducted in our laboratories in Tororo and Kampala. Most commonly short-term students are linked to laboratory projects, working with a well-established team of Ugandan researchers in Tororo or Kampala and with senior mentors from the US. Please see http://idrc-uganda.org for more information on this and other studies.
Required Qualifications: Students currently studying biology or public health. Laboratory experience preferred.