By writer to news.cornell.edu
An intercampus analysis group from Cornell and Weill Cornell Medication in New York Metropolis has been awarded a five-year, $3.65 million grant from the Nationwide Institutes of Well being (NIH) to develop a fast, cheap methodology for precisely diagnosing urinary tract infections (UTI) in kidney transplant sufferers, via molecular profiling of cell-free DNA in urine.
The group is headed by Iwijn De Vlaminck, assistant professor on the Meinig Faculty of Biomedical Engineering, together with Christopher Mason, affiliate professor of physiology and biophysics and co-director of the WorldQuant Initiative for Quantitative Prediction at Weill Cornell Medication, and Dr. Darshana Dadhania, affiliate professor of medication at Weill Cornell Medication and medical director of the Kidney and Pancreas Transplant Program at Weill Cornell Medication and NewYork-Presbyterian/Weill Cornell Medical Heart.
The investigators’ work has been supported by Cornell’s Academic Integration initiative, which goals to foster collaborations spanning Weill Cornell Medication, Cornell Tech and the Ithaca campus with a view to advance analysis and innovation throughout the college group.
The investigators met in 2017 whereas taking part within the RNA Biology Symposium, an intercampus occasion sponsored by Tutorial Integration. The group went on to obtain two of the initiative’s seed grants, main to 2 publications in 2019 and this NIH award.
“This pilot program has been actually vital in serving to us proceed to foster collaborations and usher in different individuals to assist extra analysis initiatives,” De Vlaminck mentioned. “In the end, that’s actually enabled us to make the bounce from a smaller challenge to this huge challenge.”
Urinary tract infections are a standard complication for 150 million individuals every year, together with the greater than 15,000 who obtain kidney transplants. For this work, the investigators will have a look at a potential cohort examine of 300 kidney transplant sufferers.
Utilizing expertise they beforehand developed, the group will sequence cell-free DNA from urine samples taken at a number of factors in the course of the six months following transplant, on the lookout for genomic proof of UTI. As well as, they are going to quantify whether or not urinary pathogens are inflicting damage to particular organs, a specific downside for transplant sufferers who might face organ rejection.
“Kidney transplant recipients are the best cohort for this investigation since they’re extra susceptible to an infection due to their immunosuppressed state and the place an unrecognized or untreated an infection can result in kidney failure,” Dadhania mentioned.
Cell-free DNA (cfDNA) are tiny items of DNA which can be launched from cells and flow into all through the physique. They will come from the host’s cells or from micro organism and viruses. Within the case of kidney transplant and UTI, sufferers might have cfDNA from the micro organism inflicting the an infection of their urine.
The present commonplace of analysis for UTI is urine tradition, however not all pathogens develop in tradition, leaving some infections undiagnosed or incorrectly identified. Having the ability to sequence the cfDNA from these micro organism would offer a definitive analysis, drilling down on precisely which pathogens are current, and even in what organ they’re originating.
“Urine is a dynamic and informative molecular readout of what’s taking place within the physique,” mentioned Mason, additionally an affiliate professor of computational genomics in computational biomedicine within the HRH Prince Alwaleed Bin Talal Bin Abdulaziz Al-Saud Institute for Computational Biomedicine at Weill Cornell Medication. “What’s there, and the place is it coming from? Is the an infection within the kidney or the bladder? Is it immune to antibiotics? We’re creating one instrument that may have the ability to reply all these questions.”
The purpose is to develop one methodology to check the presence or absence of a really massive vary of microorganisms.
“It’s very highly effective,” De Vlaminck mentioned. “After which on high of that, there are the host accidents that we are able to establish, and different issues like antibiotic resistance that always occurs additionally on the sequence stage. So there’s an infinite quantity of data being generated.”
“Molecular monitoring of kidney transplant recipients was pioneered at Weill Cornell Medication and is the central focus of our NIH-sponsored analysis,” mentioned co-investigator Dr. Manikkam Suthanthiran, the Stanton Griffis Distinguished Professor of Medication and Chief of Nephrology, Hypertension and Transplantation Medication at Weill Cornell Medication and NewYork-Presbyterian/Weill Cornell Medical Heart. “We’re delighted that our ongoing urinary cell mRNA profiling research of kidney allograft recipients might be complemented by profiling of urine cell free supernatants for DNA.”
Weill Cornell Medication co-investigators embrace Suthanthiran; Lars Westblade, an affiliate professor of pathology and laboratory medication; and Dr. Michael Satlin and Dr. John Lee, M.D. ’07, each assistant professors of medication.
Along with De Vlaminck, contributing from Cornell is Ilana Brito, assistant professor and the Mong Household Sesquicentennial School Fellow in Biomedical Engineering on the Meinig Faculty of Biomedical Engineering.
Geri Clark is a contract author for Weill Cornell Medication.
— to news.cornell.edu