South Asia ICEMR receives 7-year, $9.3M renewal from NIH

Pradipsinh Rathod, left, and Laura Chery, right. Dennis Wise/University of Washington

The National Institutes of Health has renewed a major grant that funds a University of Washington-led research center to understand malaria in India.

The initiative — Malaria Evolution in South Asia (MESA), first funded in 2010 — is one of 10 NIH-supported International Centers of Excellence for Malaria Research, or ICEMRs. The National Institute of Allergy and Infectious Diseases announced that it would provide $9.3 million in funds to the South Asia ICEMR over the next seven years, beginning July 1, 2017.

South Asia sits in the middle of the malaria corridor that cuts from Southeast Asia to Africa.

“India is a country of critical importance for understanding the spread of virulent malaria globally,” said Pradipsinh K. Rathod, a UW professor of chemistry and the director of the Malaria Evolution in South Asia ICEMR. “While most deaths caused by drug-resistant strains of malaria have occurred in Africa, most drug-resistant parasites arise first in Asia.”

Malaria in India remains underappreciated. The country has 1.3 billion people and more than 90% of the population live in areas where there is risk of malaria transmission. India had an estimated 13 million cases of malaria in 2015, according to the World Health Organization. Beyond that, the picture of malaria in India is one of diversity.

“There is enormous variation in the prevalence of malaria around the country — variation in levels of immunity and variation in the species of mosquitoes that spread the disease,” said Laura Chery, the South Asia ICEMR’s associate director. “Most importantly, there is unexpectedly high genetic diversity in malaria parasites that are circulating in India.”

In addition to researchers from the UW, the South Asia ICEMR also includes U.S. scientists from Harvard University, the Fred Hutchinson Cancer Research Center, the Center for Infectious Disease Research and Stanford University. But by far the largest contingent of researchers that make up the center’s efforts are the dozens of scientists, clinicians and field workers at sites across India.

“We have formed wonderful, productive partnerships with hospitals, clinics, government agencies and community members,” said Chery. “Together, we have learned to do advanced science on the ground at clinically important sites.”

Through partnerships with local hospitals and research institutes, the center currently works out of six sites across India. The locations capture the diversity of this massive country: Four sites are in eastern and northeastern India, where malaria is endemic and cases can reach as high as 50 to 100 per 1,000 people. Two other sites are on the west coast, where the prevalence of malaria can be relatively low — fewer than 1 case per 1,000 people. But these sites include urban hospitals that attract and treat large numbers of malaria patients, including migrants from other parts of the country.

“We believe that movement of people within the country can partly explain the complexity of malaria in India,” said Rathod. “However, we do not fully understand the basis for such variations.”

At each site, staff enroll patients to obtain malaria parasite samples, as well as information on each patient’s health history. From on-site laboratories in India, center staff and partners pursue a number of research projects: analyzing parasite samples for signs of drug resistance, understanding the basis for variations in disease presentation, sequencing parasite genomes and determining their genetic relatedness to one another, and testing how well different mosquito species take up various malaria strains.

In addition to setting up complex research infrastructure, in its first seven years the center has made some surprising conclusions about malaria in India. Parasites in India show more genetic diversity than parasites in the rest of the world combined, according to Rathod. As a consequence, some standard laboratory tests for drug resistance, developed elsewhere in the world, do not accurately predict whether Indian parasites will show drug resistance.

Drug resistance is a major concern in malaria. Chloroquine was once an effective drug to fight malaria. But a generation ago, malaria parasites began to evolve resistance to it, rendering it largely ineffective. Today, the drug artemisinin is considered the best treatment against malaria. But artemisinin-resistant strains of malaria already have been identified in Southeast Asia. The Indian government and the South Asia ICEMR are on the lookout for artemisinin resistance among patients in northeastern and eastern India. Beyond that, the South Asia ICEMR is looking for parasites that mutate at extraordinary rates, as seen in Southeast Asia.

“By getting a clearer picture of malaria in India, we’re ‘closing the gap’ on how this complex parasite behaves globally,” Rathod said.

For the 2017-2024 cycle, other South Asia ICEMR project leaders are Neena Valecha, director of the National Institute of Malaria Research in India, and Manoj Duraisingh at Harvard University. Additional U.S.-based senior contributors are Joseph Smith at the Center for Infectious Disease Research, Shripad Tuljapurkar at Stanford University and James Kublin and Holly Janes at the Fred Hutchinson Cancer Research Center. Additional India-based senior contributors are Anup Anvikar at National Institute of Malaria Research; Subrata Baidya at Agartala Government Medical College; D.R. Bhattacharrya and P.K. Mohapatra at Regional Medical Research Centre, NE Region; Edwin Gomes at Goa Medical College & Hospital; Sanjeeb Kakati at Assam Medical College; Ashwani Kumar at National Institute of Malaria Research, Goa Field Unit; Sanjib Mohanty and A.K. Singh at Ispat General Hospital; and Swati Patankar at Indian Institute of Technology Bombay.

For more information about Professor Rathod and his research, please visit his faculty page or the NIH NIAID South Asia ICEMR website.

Story by James Urton, UW News. Additional coverage in the July 2017 Perspectives Newsletter from the College of Arts & Sciences.

 

UW documentary features four Chemistry faculty

Professors Michael Gelb, David Ginger, Alvin Kwiram, and Pradip Rathod of the Department of Chemistry are among the notable University of Washington scientists highlighted in a new documentary released this month. “Timeless Discoveries,” a documentary made possible by the generosity of the Leonard P. & Helen M. Kammeyer Endowed Fund, highlights major breakthroughs, groundbreaking research, and practical applications revealed by the scientific community at the College of Arts & Sciences. The film, which will air on UWTV, follows professors and students as they discuss their challenges and discoveries ranging from the Hepatitis B vaccine to advances in solar energy.  The film was also featured in the Local News section of the Seattle Times.

To learn more about Professor Gelb and his research, please visit his faculty page and research group website.

To learn more about Professor Ginger and his research, please visit his faculty web page and his research group site.

To learn more about Emeritus Professor Kwiram and his research, please visit his faculty page.

To learn more about Professor Rathod and his research, visit his faculty web page.

Professor Rathod receives Medicines for Malaria Venture Project Award

Pradip Rathod, Professor of Chemistry and Adjunct Professor of Global Health, was recently awarded a Medicines for Malaria Venture (MMV) project award. The award was presented in Dar es Salaam by the President of Tanzania, Dr. Jakaya Mrisho Kikwete. Prof. Rathod received the award as a member of a group of researchers who are investigating new anti-malarial drugs. The award was presented in recognition of the international team’s “impressive progress to rapidly bring DHODH inhibitors towards clinical testing”.

Read about the MMV project award here.

To learn more about Prof. Rathod and his research, visit his faculty web page.

Pradipsinh Rathod awarded Gates Foundation grant

Pradipsinh K. Rathod, Professor of Chemistry, was awarded a $ 1,000,000 grant from the Bill & Melinda Gates Foundation as part of the next phase of Grand Challenges Explorations, an initiative to encourage bold and unconventional ideas for global health. The grant will provide continued support for Prof. Rathod’s  global health research project “Strategies to Disable Hypermutagenesis in Malaria Parasites.”

Prof. Rathod proposed that drug resistance in malaria parasite populations is driven by cellular components, a “mutasome”, that promotes acquisition of multiple mutations at target loci in the genome.  All malaria parasites may have had an ancestral, pre-existing mechanism to mutate surface proteins at extraordinary rates to avoid host immunity. However, parasite populations displaying the Accelerated Resistance to Multiple Drugs (ARMD) phenotype may have hijacked such a machinery to now make changes anywhere in the genome. Genomic studies are geared to identify genome components which help drive hypermutagenesis, and high throughput screens are being developed to directly block the process with small organic molecules. An ability to chemically disable such a mutasome during malaria therapy would improve success rates and staying power of new antimalarial drugs.   Laboratory Post-Doctoral colleagues John White and Jenny Guler, and graduate student Joseph Fowble conduct  experimental design and implementation on the GCE project in the Rathod laboratory.

Grand Challenges Explorations is a five-year, $100 million initiative of the Gates Foundation to promote innovation in global health. For more information, visit  http://www.grandchallenges.org/explorations.

To learn more about Prof. Rathod’s research, visit his faculty page.

Pictured: Prof. Rathod and Dr. Jennifer Guler in the lab (photo by Mary Levin).

Pradip Rathod receives Gates Foundation grant

Professor Pradipsinh Rathod was one of 104 recipients of a grant through the Bill & Melinda Gates Foundation‘s new initiative, Grand Challenges Explorations in Global Health. Rathod’s grant will support a project titled “Strategies to Disable Hypermutagenesis in Malaria Parasites,” which targets components of the malaria genome and develops partner drugs to disable parasite hypermutagenesis, allowing older methods of treatment to be effective against the disease.

The Gates Foundation believes that “creative, unorthodox thinking is essential to overcoming the most persistent challenges in global health,” and the Grand Challenges Explorations initiative is designed to “foster innovation in global health research and expand the pipeline of ideas that merit further exploration.” The initiative features an accelerated grant-making process with short two-page applications requiring no preliminary data. Initial grants of approximately $100,000 are awarded, with the possibility of additional funding ($1 million or more) for projects that show promise. The projects selected fit into the fourteen “grand challenges” set forth by the Gates Foundation, which address seven long-term goals to improve health in the developing world, such as creating new vaccines, improving nutrition, and establishing quantitative assessments of overall population health.

To view the full article in UWeek, please visit: GCGH article.

The awarding of the GCGH grants was covered by the local press, with articles in the Seattle Post-Intelligencer and the Seattle Times.

For more information about Pradip Rathod and his research, please visit his faculty page.

Pradip Rathod and research team receive MMV grant

Professor Pradipsinh Rathod is part of a team of scientists who have received a grant from the Medicines for Malaria Venture (MMV). The group received funding for a five-year project, “Optimizing novel Dihydroorotate Dehydrogenase Inhibitors for Treating Malaria.” The DHODH project team also has investigators from the University of Texas Southwestern Medical Center and Monash University.

For more information about the MMV DHODH project, please visit the MMV DHODH page.

For more information about Pradip Rathod and his research, please visit his faculty page.