Found in translation

With the university’s largest-ever grant, researchers seek to close the gap between lab discovery and patient care

 

BY DANIEL ROBISON

For many people, artificial intelligence is the next big thing. For Brennan Flannery, it’s a life-saving thing.

As a Ph.D. candidate in Case Western Reserve University’s Department of Biomedical Engineering, Flannery is creating a clinical tool that uses machine-learning models to analyze radiology and pathology images to spot kidney cancer and kidney failure. The approach could be especially beneficial for those affected by diabetes and high blood pressure— conditions more likely to afflict Black individuals, women, and older adults. “Many people with these conditions often don’t get diagnosed until it’s too late for impactful treatment,” Flannery said. “AI can help us spot kidney issues much earlier, so patients get proper care sooner or on a transplant list with more time.”

Soon after developing his idea to create this software for common healthcare settings, Flannery began the process of securing a provisional patent—a first step in translational research, which aims to bring laboratory work to the real world faster.

His efforts are aided by two federally funded initiatives at Case Western Reserve that facilitate translational research in the university's Clinical and Translational Science Collaborative and National Center for Regenerative Medicine programs. Flannery receives personalized guidance from industry experts, as a School of Medicine Translational Fellow; he's trained in product development (IP) and evaluating markets, among other topics.

Both initiatives are part of the Clinical and Translational Science Collaborative (CTSC) of Northern Ohio, a partnership between the university and affiliated healthcare institutions to spur translational efforts.

"One of the reasons I came to CWRU was this huge focus on developing new technologies to therapies," said Flannery. "It's important to me that my research directly helps people."

Closer to the patient

In August, the NIH awarded the CTSC a seven-year, $64.3 million grant—the largest single award in the university's history— that builds on $175 million in related funding since the collaborative's founding in 2007. The CTSC of Northern Ohio is one of 60 Clinical and Translational Science Award hubs around the country. The NIH now awards around an average of 10 efforts that are badly needed: According to the NIH, fewer treatments require an average of 10.5 years to develop and fail 95 percent of the time.

"There are thousands of diseases and only hundreds of treatments, so there's a need for urgency for research breakthroughs and reach patients and communities," said Grace McComsey, MD, vice dean for clinical and translational research at the medical school and the principal investigator of the CTSC.

5 The number of startup companies, on average launched annually by faculty, staff, and students based on CWRU technology

#24CWRU’s standing globally for utility patents 2022 U.S. Patent and Trademark Office data

Since the mid-2000s, the School of Medicine and CWRU have established an infrastructure and entrepreneurial culture to drive discoveries from “bench to bedside.” 

Faculty and students have access to a network of resources to navigate the complex processes of protecting IP, licensing technology, and creating companies. They also receive guidance to traverse the tightly regulated world of biomedical products, including drugs, diagnostics, and medical devices. 

By many measures, the effort is yielding results. Led by School of Medicine faculty, Case Western Reserve ranked #24 among universities worldwide for utility patents, according to 2022 data from the U.S. Patent and Trademark Office—a ranking that has steadily improved over the last decade and places the institution ahead of universities such as Yale, Carnegie Mellon, and Columbia.

Since the CTSC began in 2007, Case Western Reserve has tripled the number of biomedical companies—many with significant valuations—launched each year from technology and treatments developed in its labs. Meanwhile, dozens of discoveries at the university have been licensed to third-party companies.

What is Translation

Translational research turns scientific discoveries into real-world health solutions. It bridges the gap between lab research and practical applications— creating tools, treatments, and interventions for better healthcare and behavioral improvements.

“The fastest, most efficient route for reaching the patient through a new invention or discovery is often by selling technology to a company or creating a startup—it creates the incentive to reach the market quickly,” said Michael Oakes, Ph.D., the university’s senior vice president for research and technology management. “This is why our entrepreneurial ecosystem is so important: Our collective expertise and relationships find the right home for innovations that help people.”

Targeting disparities through translation

In past grant cycles, the CTSC focused on establishing the infrastructure and workforce to bridge the gap between laboratory research and patient care. However, this grant cycle takes a different approach, evident in its theme: “Catalyzing Linkages to Equity in Health,” or CLE Health. While the CTSC has long funded clinical research focused on underrepresented minority groups— leading to significant changes in treatment for hypertension and other chronic diseases—the consortium will delve deeper into the factors contributing to widespread health disparities among different communities.

“Tons of money is put into research, but in most cases, it’s not improving health at the community level,” said McComsey. “The missing innovation is translating things that are known to work in humans to broader communities—what we call ‘late translation.’” Decades of evidence link disparities in life expectancy, infant mortality, and chronic diseases to social determinants of health—economic and environmental factors that extend beyond medical care, such as housing, access to nutritious food, dependable transportation, education, and job opportunities.

 New CTSC-funded research projects—ranging from small pilot grants to multi-year awards—will aim to better understand the root causes of health disparities while developing effective strategies to counteract them and improve outcomes.

“Often, researchers need a little bit of funding to get up and running so they can gather data, test ideas, and move research forward,” said William Schiemann, Ph.D., vice dean for research at the School of Medicine and leader of its Office of Research Administration. “The CTSC gets many of these projects off the ground.”

The CTSC will prioritize recruiting populations that are typically underrepresented in clinical research— specifically Black Americans, Hispanics, LGBT+ individuals, adults over age 75, people with disabilities, and rural residents.

Lack of minority group inclusion in clinical trials has long limited data on the safety and effectiveness of new treatments for diverse populations— and created a shortage of trust in medical practices. To ensure research reaches these patient populations, particularly in rural areas, the collaborative is adding two new partners, the University of Toledo and Northeast Ohio Medical University. 

They join Cleveland Clinic, the MetroHealth System, University Hospitals, and the Louis Stokes VA Medical Center as affiliates. 

The CTSC also is expanding workforce development initiatives to train and educate community members to be part of the research teams as study coordinators, regulatory specialists, and community health workers.

 The approach will help bring in more people from different backgrounds and communities to take part in new research and leadership roles, “which will result in more interventions that promote health to more people more quickly,” said Michael Konstan, MD (WRC ’78, MED’82), professor of pediatrics at the School of Medicine and the former principal investigator of the CTSC. 

Another goal: creating opportunities for community organizations and local small businesses to participate—including reviewing and providing feedback on research projects.

 “Community voices should be present in the research so when translational activities move forward, they have the most impact because we better understand a range of lived experiences,” said Shari Bolen, MD, an associate professor in the Department of Population and Quantitative Health Sciences who is leading community and stakeholder engagement for the CTSC. 

To prepare researchers for working more closely with community partners, Gelise Thomas, JD, is creating a new programmatic foundation for the CTSC—including training that provides regulatory guidance for clinical trials, helps develop studies that foster inclusive partnerships, and integrates community health workers. 

“We are at a point now with this grant cycle where it’s the ultimate level of accountability. If you weren’t thinking about inclusion and diversity and accessibility before, you have no choice but to now,” said Thomas, assistant director of strategic DEI and health disparities with the CTSC. 

“That will require a lot of willingness, openness, and vulnerability that the scientific community historically has not been called to show,” said Thomas. “It’s an opportunity and an obligation. We’re all at the table—and the tools, resources, and people are here, ready to go.”

Recent examples of entrepreneurial success

  1. Rodeo Therapeutics, a drug-development startup founded by School of Medicine researchers—Sanford Markowitz, MD, Ph.D., the Markowitz-Ingalls Professor of Cancer Genetics and a Distinguished University Professor, and Stanton L. Gerson, MD, dean and senior vice president for medical affairs—was acquired in 2021 by Amgen, a publicly traded international biopharmaceutical company, for $55 million, with additional milestone payments of $666 million possible.
  2. Lucid Diagnostics, a company producing esophageal cancer tests—derived from research by Markowitz, Amitabh Chak, Ph.D., a professor of medicine, and Joseph Willis, Ph.D., a professor of pathology, and University Hospitals physicians—concluded a $70 million initial public offering on the Nasdaq Global Market in 2021.
  3. NeoIndicate LLC signed an exclusive agreement with the university in 2022 to commercialize an imaging agent that lights up tumor cells, helping neurosurgeons achieve more precise surgical removal of glioblastoma and other malignant brain tumors. The startup’s founder and chief scientific officer, Susann Brady-Kalnay, Ph.D. a professor in the Department of Molecular Biology and Microbiology at the medical school—discovered the biomarker and created the imaging agents that detect it.
  4. Convelo Therapeutics, a biotechnology firm that focuses on creating regenerative medicine for neurological disorders—based on research by Paul Tesar, Ph.D., the Dr. Donald and Ruth Weber Goodman Professor of Innovative Therapeutics, and Drew Adams, Ph.D., an associate professor of genetics and genome sciences entered into a partnership with Genentech in 2019.

A critical catalyst

In 2014, Umut Gurkan, PhD, received a small CTSC grant to study the viability of a promising blood-testing technology.

 “CTSC funding was the critical catalyst,” said Gurkan, the Wilbert J. Austin Professor of Engineering, who also holds appointments in biomedical engineering and orthopedics at the School of Medicine and is a member of the Case Comprehensive Cancer Center. “Once I received the CTSC funding, it was a tipping point. The rest was one thing leading to another, like a domino effect.”

 With the help of additional funding—including an award from the Case-Coulter Translational Research Program Gurkan developed HemeChip, a point-of-care diagnostic tool tailored for use in low-income countries that can diagnose sickle cell disease and others. In 2018, Hemex Health Inc. licensed the technology. Now known as Gazelle by HemexHealth, the testing device based on Gurkan’s research is now available in more than 35 countries.

“Through the CTSC,” said Gurkan, “I was able to access the expertise that is needed for regulatory processes, customer discovery, market analysis, manufacturing, and support to take a technology from the lab to the outside world.”

Translation in motion

Despite an overall decline in cigarette use in recent decades, historically disadvantaged populations haven’t seen the same pace of smoking cessation—a discrepancy that hinders the broader public health benefits of reducing tobacco consumption.

And data shows that groups with the highest rates of smoking are also much more likely to be food insecure.

 “Most people who smoke say they do so to relieve stress—and food insecurity is stressful,” said Jin Kim-Mozeleski, Ph.D., an assistant professor in the Department of Population and Quantitative Health Sciences. “They also smoke to reduce their appetite or deal with feelings of hunger.” 

To test methods for how to reduce tobacco use in these groups, Kim-Mozeleski received a CTSC Pilot Award, which aims to fuel early-stage research projects and prepare investigators to expand their studies. 

With the $50,000 grant, Kim-Mozeleski developed a study examining whether reducing food insecurity can help smokers successfully quit.

“It’s novel research,” said Kim-Mozeleski, “because smoking cessation services and treatments have not traditionally incorporated the role of social determinants of health and how those can impact outcomes.” 

The study, conducted with the Institute for H.O.P.E. at MetroHealth—a CTSC affiliate— linked participants to community health workers and patient navigators, who provided evidence-based treatments for tobacco cessation. 

Half of the participants also received an additional financial benefit to help offset the cost of food while they tried to quit smoking. Preliminary results show this group was more likely to make a serious attempt to quit, had longer lengths of abstinence from smoking, and, if the data holds true, was more likely to successfully quit. 

With the pilot complete, Kim-Mozeleski is applying for larger grants to do a full-scale study. “There is such a gap in this area,” she said. “The pilot award enabled us to collect valuable input that’s now guiding our research.”