Posted in | Bionanotechnology

Research Grant to Understand Biological Mechanisms of HIV Resistance Using Nanodevices

Published on November 2, 2012 at 6:32 AM

Weill Cornell Medical College announced today that it is a Grand Challenges Explorations winner, an initiative funded by the Bill & Melinda Gates Foundation.

Researchers at Weill Cornell have been awarded three research grants totaling more than $1.5 million. Weill Cornell's Dr. Juan R. Cubillos-Ruiz, a postdoctoral research associate in medicine in the laboratory of Dean Dr. Laurie H. Glimcher, will pursue an innovative global health and development research project titled, "Tailored Nanodevices to Understand Resistance Against HIV," Dr. Carl Nathan, chairman of microbiology and immunology and R.A. Rees Pritchett Professor of Microbiology, will investigate "Sequestration and asymmetric distribution of irreversibly oxidized proteins in Mycobacterium tuberculosis (Mtb)" and Dr. Kyu Rhee, associate professor of medicine and microbiology and immunology, will examine "Mining metabolosomes: A biochemical blueprint to new drug targets against non-replicating Mtb."

"Weill Cornell is honored to be selected as a multiple award winner of Grand Challenges Explorations grants for our groundbreaking research initiatives to combat devastating diseases like HIV and TB," says Dr. Glimcher, the Stephen and Suzanne Weiss Dean of Weill Cornell Medical College and provost for medical affairs of Cornell University. "We thank the Bill & Melinda Gates Foundation for continuing its generous support of our pioneering and innovative researchers whose work is truly making a difference on a global level."

"Our research team is thrilled to receive this prestigious award from the Bill & Melinda Gates Foundation in support of our HIV research efforts," says Dr. Cubillos-Ruiz, a senior postdoctoral fellow in the laboratory of Dr. Glimcher. "We aim to use cutting-edge nanotechnology tools to unveil the biological mechanisms that some individuals have to exert powerful resistance against HIV. We hope our novel research strategy paves the way for designing and developing a functional cure for HIV."

"Three to four people die of tuberculosis each minute. Dr. Rhee and I sincerely thank the Bill & Melinda Gates Foundation for its dedication to improving the mortality rate and health of people in our nation and around the globe with TB through innovative research projects," says Dr. Nathan. "With the Foundation's help, we hope to improve our understanding of TB and find more effective and faster-acting drug therapies for TB with shorter treatment cycles."

Grand Challenges Explorations (GCE) funds individuals worldwide who are taking innovative approaches to some of the world's toughest and persistent global health and development challenges. GCE invests in the early stages of bold ideas that have real potential to solve the problems people in the developing world face every day. Dr. Cubillos-Ruiz, Dr. Nathan and Dr. Rhee's projects are three of over 80 Grand Challenges Explorations Round 9 grants announced today by the Bill & Melinda Gates Foundation.

"Investments in innovative global health research are already paying off," said Chris Wilson, director of Global Health Discovery and Translational Sciences at the Bill & Melinda Gates Foundation. "We continue to be impressed by the novelty and innovative spirit of Grand Challenges Explorations projects and are enthusiastic about this exciting research. These investments hold real potential to yield new solutions to improve the health of millions of people in the developing world, and ensure that everyone has the chance to live a healthy productive life."

To receive funding, Dr. Cubillos-Ruiz, Dr. Nathan and Dr. Rhee and other Grand Challenges Explorations Round 9 winners demonstrated in a two-page online application a creative idea in one of five critical global heath and development topic areas that included agriculture development, immunization and communications. Applications for the current open round, Grand Challenges Explorations Round 10, will be accepted through November 7, 2012.

Dr. Cubillos-Ruiz and his team's Phase I $100,000 funded research project will use a highly innovative nanopore-based assay to identify novel biomarkers reflecting the multifactorial processes that trigger potent HIV suppression. Dissecting these unique molecular signatures may enable the research team to design and develop improved clinical strategies for enhancing resistance against HIV. According to Dr. Cubillos-Ruiz, a small proportion of HIV infected individuals called "elite controllers" demonstrate "spontaneous" long-term control over the virus in the absence of treatment. However, the biological mechanisms underlying this important phenomenon remain poorly understood. Dr. Ruiz will work in close collaboration with other scientists at Weill Cornell, The Methodist Hospital in Houston and The Ragon Institute of MGH, MIT and Harvard.

Dr. Nathan and his research team's Phase II $646,688 funded project will test their hypothesis that tuberculosis is able to exit latency by distributing damaged proteins to a senescent cell lineage, while more functional proteins are diverted to a lineage with full replication potential. His team believes regulating this post-latency cell division could be the target of novel drug therapies. Phase I of Dr. Nathan's study used biochemical methods and time lapse photomicroscopy to demonstrate that Mtb accumulates irreversibly oxidized proteins when its replication is blocked. These proteins then form small aggregates that fuse into larger ones. One member of the progeny pair retains the aggregates when cell division resumes. The new Phase II study will identify genes that control this process. Dr. Nathan's research team includes Weill Cornell's Julien Vaubourgeix and Dr. Gang Lin.

Dr. Rhee's Phase II $782,724 funded research project will test the theory that tuberculosis utilizes metabolosomes, which are protein-based metabolic structures, to enter into, maintain and exit from latency. Understanding how metabolosomes work will aid in development of drugs that target TB. This project's Phase I research demonstrated that "latent" or non-replicating Mtb undergo a metabolic remodeling that is accompanied by the reversible formation of enzyme-based protein structures (metabolosomes). In Phase II, Rhee and colleagues will characterize and test the essentiality of a prototypic metabolosome as a potential target whose inhibition could lead to development of new and highly needed treatment-shortening drugs.

About Dr. Juan Cubillos-Ruiz
Dr. Cubillos-Ruiz currently serves as senior postdoctoral fellow in the laboratory of Dean Laurie H. Glimcher at Weill Cornell Medical College. His expertise and research focuses on tumor immunotherapy, viral immunology and biomarker discovery. He previously worked at Harvard University and his postdoctoral research has been supported by awards from the Cancer Research Institute and The Ragon Institute of MGH, MIT and Harvard. He received his Ph.D. in Microbiology and Immunology from Dartmouth Medical School (Hanover, NH) and his undergraduate degree from Los Andes University in Bogota, Colombia.

About Dr. Carl Nathan
One of today's pre-eminent immunologists, Dr. Nathan serves as the R.A. Rees Pritchett Professor of Microbiology and chairman of the Department of Microbiology and Immunology and the director of The Abby and Howard Milstein Program in the Chemical Biology of Infectious Disease at Weill Cornell Medical College. He is a member of the National Academy of Sciences, the Institute of Medicine and the American Academy of Microbiology, as well as the recipient of the 2009 Robert Koch Prize for his research on how the immune system protects us from bacterial pathogens. Dr. Nathan studies host-pathogen interactions along with an interdisciplinary team that seeks to bring immunology, microbiology, biochemistry, structural biology and chemical biology to bear on tuberculosis. His work is supported by NIH, the Bill & Melinda Gates Foundation and the Abby and Howard P. Milstein Program in Chemical Biology of Infectious Diseases. Dr. Nathan received his undergraduate degree from Harvard University and his medical degree from Harvard Medical School. He joined the Weill Cornell faculty in 1985.

About Dr. Kyu Rhee
Dr. Rhee currently serves as associate professor of medicine in the Division of Infectious Diseases, associate professor of microbiology and immunology at Weill Cornell and associate attending physician at NewYork-Presbyterian Hospital/Weill Cornell Medical Center. His clinical interests are in the areas of tuberculosis and antibiotic pharmacology. His major research interests are in elucidating the basic physiology of Mycobacterium tuberculosis, the causative agent of TB, and identification of novel drug targets. Dr. Rhee received his undergraduate degree from Cornell University and his M.D. and Ph.D. degrees from the University of California, Irvine, followed by clinical training in internal medicine and infectious diseases at Weill Cornell, where he has remained on the faculty since 2005, and also co-directs the Medical Research Residency track in internal medicine.

About Grand Challenges Explorations
Grand Challenges Explorations is a US$100 million initiative funded by the Bill & Melinda Gates Foundation. Launched in 2008, over 700 people in 45 countries have received Grand Challenges Explorations grants. The grant program is open to anyone from any discipline and from any organization. The initiative uses an agile, accelerated grant-making process with short two-page online applications and no preliminary data required. Initial grants of US$100,000 are awarded two times a year. Successful projects have the opportunity to receive a follow-on grant of up to US$1 million.

Weill Cornell Medical College
Weill Cornell Medical College, Cornell University's medical school located in New York City, is committed to excellence in research, teaching, patient care and the advancement of the art and science of medicine, locally, nationally and globally. Physicians and scientists of Weill Cornell Medical College are engaged in cutting-edge research from bench to bedside, aimed at unlocking mysteries of the human body in health and sickness and toward developing new treatments and prevention strategies. In its commitment to global health and education, Weill Cornell has a strong presence in places such as Qatar, Tanzania, Haiti, Brazil, Austria and Turkey. Through the historic Weill Cornell Medical College in Qatar, the Medical College is the first in the U.S. to offer its M.D. degree overseas. Weill Cornell is the birthplace of many medical advances -- including the development of the Pap test for cervical cancer, the synthesis of penicillin, the first successful embryo-biopsy pregnancy and birth in the U.S., the first clinical trial of gene therapy for Parkinson's disease, and most recently, the world's first successful use of deep brain stimulation to treat a minimally conscious brain-injured patient. Weill Cornell Medical College is affiliated with NewYork-Presbyterian Hospital, where its faculty provides comprehensive patient care at NewYork-Presbyterian Hospital/Weill Cornell Medical Center. The Medical College is also affiliated with the Methodist Hospital in Houston.

Source: http://weill.cornell.edu

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