The Herbert Irving Comprehensive Cancer Center (HICCC) has awarded three new pilot grants to Columbia University faculty members whose research ideas are targeting accelerated solutions to combat COVID-19.

The three winning COVID-19 research projects are being led by: Sagi Shapira,PhD, assistant professor of systems biology at Columbia’s Vagelos College of Physicians & Surgeons and Nicholas Tatonetti, PhD, associate professor of bioinformatics at VP&S and HICCC member; Samuel Sia, PhD, professor of biomedical engineering at Columbia Engineering; and Hee Won Yang, PhD and Alejandro Chavez, MD, PhD, both members of the HICCC and assistant professors of pathology and cell biology at VP&S. The pilot grants are the first set of COVID-19 research awards administered by the HICCC and are made possible, in part, through a generous donation from Marilyn Skony Stamm, who sits on the HICCC Cancer Advisory Council and is president and CEO of Stamm International.

The winning projects represent a diverse range of COVID-19 research: exploring a drug screening platform to rapidly identify treatments against SARS-CoV-2 and also other coronaviruses; uncovering how SARS-CoV-2 causes more severe disease in some people using a combination of patient electronic health data and a computational method that identifies key strategies used by the virus to multiply; and the development of a rapid, easy-to-use, low-cost device for home-based antibody testing and mobile app that explains test results to the user.

“In the face of this pandemic, we are inspired and grateful for all of our essential clinical physicians and health care providers who are on the front lines taking care of our patients and communities,” says Anil K. Rustgi, MD, director of the HICCC. “Our researchers, and many others, are in the background supporting these frontline efforts, shifting their focus towards COVID-19, working to find new vaccines, therapies and other measures. We developed these pilot grants to support and help launch those efforts, in collaboration with the Irving Institute for Clinical and Translational Research.”

Skony Stamm hopes the funding dedicated to therapeutics will help fast track the development of medicines. Like many other business leaders, she has found herself in the throes of the COVID-19 pandemic, working quickly to ensure firsthand the safety of her employees and making swift changes to conduct business amid the present-day difficulties. Her support of the HICCC pilot grants for COVID-19 research is rooted personally. 

“People near and dear to me started coming down with [the virus],” says Skony Stamm. “I saw what was happening in New York. This was really close to home for me. I had to do something.”

The HICCC pilot grants for COVID-19, announced about two weeks after the pandemic declaration, garnered some 60 applications, and from start to finish, were launched, reviewed, and administered in just a little over six weeks.

“There was incredible energy around this effort, and we had a tremendous response across the University,” says Emer Smyth, PhD, associate director of administration at the HICCC. “We held a rapid review process and followed a very compressed time line to bring these funds as quickly as possible to researchers who are working against this pandemic.”

The pilot grant recipients were asked to focus on research that will have an impact on COVID-19 in the short term and were given $50,000 and one year to carry out the work. The HICCC’s research pilot grant program funds out-of-the-box, collaborative research on topics or problems that cross disciplines and unite researchers. The program, a mainstay of the HICCC’s commitment to fostering and developing innovative research , administers new pilot grants year-round.

COVID-19 innovative solutions:

“Identification of Adverse SARS-CoV-2 Infection Outcome Determinants”
Lead Investigator: Sagi Shapira, PhD
Co-PI: Nicholas Tatonetti, PhD

Nicholas Tatonetti (left) and Sagi Shapira

Drs. Shapira and Tatonetti will work on accurately identifying pathophysiological factors that modulate SARS-CoV-2 infection and explain variability in disease outcomes. Identifying determinants of COVID-19 severity is critical for patient triaging decisions, choice of treatments, and setting of appropriate social public health measures. Knowledge of the precise molecular interactions that occur during viral life cycles can provide valuable clues about disease determinants. In earlier work, the researchers used this principle to guide discovery of novel clinical prognosticators of SARS-CoV-2 infection. In a retrospective observational study of more than 11,000 patients, they uncovered that a history of macular degeneration and history of coagulation disorders—regardless of the patient’s age or sex—are associated with poor clinical outcome in SARS-CoV-2 infected patients. They went on to identify putative genetic markers of susceptibility in regulators of the complement system, a critical regulator of immune responses to microbial threats, and blood coagulation system. In this proposal, the researchers will leverage their multimodal analytical approach to combine molecular information from virus protein structure-function analysis with clinical informatics and genomics from patient records in New York and the United Kingdom to reveal determinants and predictors of immunity, susceptibility, and clinical outcome associated with SARS-CoV-2 infection.

“Smartphone-enabled Home Serology Tests for Large-scale, Accurate, and Trackable COVID-19 Testing and Surveillance”
Lead Investigator: Samuel Sia, PhD

Samuel Sia

A rapid antibody test for COVID-19 will be highly valuable and could better inform us of true disease prevalence, including an accurate understanding of mortality rate, support contact tracing for individuals who are informed of their past infection status, help track epidemiological spread, and help millions of Americans return to work with at least presumed short-term immunity. In this work, Dr. Sia’s team will prototype a rapid and sensitive testing kit for measuring antibodies of SARS-CoV-2 and develop a smartphone app that can quickly and accurately scan in test results, with real-time communications and explanation of the results to the user. The prototype will be designed as a low-cost, home-based testing system with user-friendly instructions for consumers and easy-to-understand results. To address this need in COVID-19, the Sia lab will leverage previous work in rapid HIV tests for self-testing and their expertise in devising innovative and mobile diagnostic technologies.

“Novel Technologies to Identify SARS-CoV-2 Therapeutics”
Lead Investigator: Hee Won Yang, PhD
Co-PI: Alejandro Chavez, MD, PhD

Hee Won Yang (left) and Alejandro Chavez

There is an urgent need for therapies to combat SARS-CoV-2, but also to fight other coronaviruses. Several hundred other coronaviruses are in active circulation right now within animals, some of which have the potential to infect humans. Coronavirus 3CL proteases are present within all coronaviruses and play essential roles in viral replication, making them an ideal drug target. Drs. Yang and Chavez propose to develop and apply a novel drug screening platform to identify inhibitors of these viral proteases. Building upon existing work, the team will develop a high throughput image-based screening platform to screen a chemical library of over 1,000 FDA-approved drugs to identify novel SARS-CoV-2 3CL protease inhibitors. They intend to also expand this approach to include other coronavirus 3CL proteases, and use this to search for broad 3CL protease inhibitors within the compounds identified in the first phase of their project. Their aim is to provide new therapeutic strategies for SARS-CoV-2 and other coronaviruses.

-Melanie A. Farmer