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Mount Sinai leads unprecedented attempt to discover rules for assembling human tissue

Submitted by on 27 December, 2020 – 4:32 pm
Researchers at Mount Sinai School of Medicine and two other academic institutions have received federal funding for systematic functional kidney tissue from human tissue modeling into a computer. If successful, the research that integrates several emerging technologies, including virtual modeling and nanofabrication tissues, could lead to a more predictable way for researchers to engineer tissue outside the body and, consequently, to detect new drugs .

To finance the project, called the underlying dynamics of tissue integrity, the National Institutes of Health (NIH) has awarded a five-year, $ 6 million grant from its Research Projects transformer (T-R01) program. T-R01 is a new program designed to support exceptionally innovative research initiatives whose results provided have a major impact in general, important problems in biomedical and / or behavioral research. T-R01-42 overall winners of this year, receive part of their funding from the Recovery and Reinvestment Act.

The leader of this multi-project principal investigator, Ravi Iyengar, PhD, Director of Experimental Therapeutics Institute (TSI) at the Mount Sinai School of Medicine, said the establishment of an assembly of tissues requires your computer to solve a problem that has existed since pathologists began to examine the human cells under a microscope.

“Pathologists are likely to characterize the disease in patients by studying the shape of cells and tissues, and its diagnosis has always been largely empirical,” said Dr. Iyengar, who is also Dorothy H. and Lewis Rosenstiel Professor and Chair of Pharmacology and Systems Therapeutics, and Professor of Oncology and Psychiatry Sciences, Mount Sinai School of Medicine. “Nobody knows why change the forms of cells or the rules by which tissues are organized. We want to start getting a handle on this study by the kidney, and have required the collaboration of several different disciplines.”

Scientists plan to focus on the podocyte, a specialized renal cell found in the basement membrane of the body and controls the filtration of small protein molecules. A violation of this filtration barrier is a major cause of kidney disease that occurs frequently among patients with diabetes, HIV, and hypertension. African-Americans with hypertension are four times more likely than whites to develop hypertension, kidney disease, a condition that currently has no cure and eventually may require dialysis.

According to Dr. Iyengar, discovering the underlying principles of the Assembly of tissues, as he and his colleagues plan to do here, and with a more reliable method for mounting tissue within a nanofabricated device would have a large clinical impact . “The lack of tissue engineered devices in vitro, or outside the cell body, is a major obstacle in testing new drugs,” he said. “If the experiment works and we have a methodology for setting up these tissues within nanofabricated devices, this could become a useful screening method for discovery of new drugs for kidney disease.

“The efforts of the team of Dr. Iyengar, to better understand kidney function at the cellular level will help to therapeutic research,” said Dennis S. Charney, MD, the Anne and Joel Ehrenkranz Dean of Mount Sinai School of Medicine and Executive Vice President for Academic Affairs at The Mount Sinai Medical Center. “Mount Sinai, where the infrastructure is designed to foster translational research, is tailored for collaborative research projects such as this.”

Much of the research was carried out in the TSI, the Mount Sinai center for the development of new drugs and devices through the integration of multiple facets of therapeutic research, and Systems Biology NIGMS-funded Center of New York (SBCNY ), Dr. Iyengar also directs and is also based at Mount Sinai. SBCNY researchers to study a system level of molecular interactions in cells and its relationship to the physiological function of tissues and organs.

“Dr. Iyengar has taken an extraordinary opportunity, the ability to exploit the biology of systems to facilitate the development of new drugs and diagnostic tools,” said Kenneth L. Davis, MD, President and CEO of The Mount Sinai Medical Center. “His work has the potential to create a new scientific paradigm.”

The other principal investigators at Mount Sinai include John Cijiang He, MD, PhD, Associate Professor of Medicine and Nephrology and Associate Professor of Pharmacology and Systems Therapeutics, and Susana Neves, PhD, Postdoctoral Fellow in the Department of Pharmacology and Systems Therapeutics .

Otros dos investigadores principales participación en la concesión de préstamos y su experiencia son James C. Hone, PhD, Columbia University, who design and manufacture the micro or nanoscale devices, and Leslie M. Loew, PhD, who pioneered the development of a computational modeling platform at the University of Connecticut Health Center called virtual cell. Dr. Loew develop computer models of how cells interact in the kidney tissues.

These computational models, or virtual tissue, will be the basis for the design of the device to recreate the renal function. The hope is to learn the rules of tissue organization as the team refines the test device through the computer models and images flow signals in the tissue cells reassembled from mouse and human cells.

Commenting on the award, Francis S. Collins, MD, PhD, director of NIH, said the T-R01 program “is intended to support research that has the potential to transform the way we think about science and behavior, so the recipients represent an elite few with truly bold ideas. The competition for the awards was fierce, and very high standards. “

Source: The Mount Sinai Hospital

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