CLP-Feinberg Convergence Initiatives
Convergence Initiatives stretch across Northwestern’s Evanston and Chicago campuses to propel new protein-based discoveries and apply them to the most intractable medical challenges.
Accelerating Team Science
CLP has set aggressive goals to conquer diseases that have a compelling clinical need by developing new proteoform signatures of health and disease across multiple tissue types and disease mechanisms.To acheive it’s bold mission, CLP has developed a series of Convergence Research Initiatives which bring together teams of Northwestern chemists, life scientists and engineers, with clinicians in Northwestern’s Feinberg School of Medicine (FSM), to provide a holistic approach to critical clinical problems that stretch from the lab bench to the patient bedside. Convergence Initiatives propel CLP towards clinical impact by enabling team members to jointly conceptualize how protein-based discovery can be applied to unresolved medical challenges.
For example:
Multidisciplinary push toward treatment of ALS
A CLP-paired chemist and neurologist identified the first drug-like compound, NU-9, to improve the health of upper motor neurons. Studying proteins involved in ALS, the team identified a mutation found in 90% of people living with the disease, and they determined that a grouping of these abnormal proteins instigates an attack to destroy motor neurons. Using mouse models, neurologists demonstrated how NU-9 stopped the attack and even helped repair some of the damage.
Using proteoform signatures in blood to predict organ transplant rejection
CLP partnered with FSM transplant surgeons to leverage proteoform and organ transplant expertise. They used groundbreaking CLP methods to identify a panel of unique proteoforms that are associated with early-stage transplant rejection in immune cell proteins from post-surgical patients. This convergence of proteomics with clinical insights has the potential to support life-saving clinical decision making to accelerate treatments that block transplant rejection.
Conquering Cancer and Neurodegenerative Disease
Over the next five years, through its Convergence Initiatives, CLP will address cancer and neurodegenerative diseases, including ALS, Alzheimer’s disease and Parkinson’s disease. Building on our success in drug discovery with advanced proteomic platforms, interdisciplinary teams of CLP investigators and clinicians will identify more precise targets and develop more sensitive diagnostics that might lead to earlier diagnosis and potential treatment for these diseases. These efforts will advance technical and program readiness for major federal and foundation funding and pave the way for an expanded focus to include kidney disease, transplant rejection, liver disease and cirrhosis, and heart disease.
Our activities will inform the development of drugs for existing targets, show utility for proteoforms as companion diagnostics, and discover new therapeutic targets. By implementing chemical and top-down proteomics in collaboration with interdisciplinary teams and advance technical and program readiness for major federal and foundation funding. We will identify unique proteoform targets associated with disease development and progression. New proteoform data will enable more accurate characterization of binding sites, protein complexes, and be deployed as a starting point for high throughput screening. New data will be provided quarterly, and the group will meet regularly to identify targets of greatest potential impact.
How It Works
Pilot Funding
CLP provides pilot funding (backed by generous donors) for dream teams of CLP’s medicinal chemists, chemical biologists, pharmacologists and Feinberg clinicians focused on neurodegenerative diseases and cancer.
Proteoform Identification
Researchers analyze tissue and blood obtained through collaboration with FSM researchers using top-down mass spectrometry methods to determine the unique proteoform signatures of these diseases.
Drug Development
CLP integrates platforms for chemical proteomics for target identification, validation, and engagement with proteoform target mapping, then deploys its medicinal chemistry capabilities to advance candidate small molecules.
“What happens with physicists, chemists, geneticists, cancer biologists meet? A future without cancer starts to become a reality.”
Marcelo G Bonini, PhD, Professor of Medicine (Hematology and Oncology) and Biochemistry and Molecular Genetics
CLP-LURIE CANCER CENTER CONVERGENCE WORKSHOP
Cancer Genomics and Redox Epigenetics
On June 29, 2023, the Institute hosted the CLP-Lurie Cancer Center Convergence Workshop to bring together CLP and Lurie Cancer researchers to discuss some of Northwestern’s most innovative cancer epigenetics research and methods and opportunities for collaboration. The online program covered cutting-edge physical sciences approaches and technologies developed by CLP faculty and clinically relevant cancer models, mechanisms, and targets identified by Lurie Cancer Center researchers.
“CLP creates an environment where great minds unite. Neurodegenerative diseases are very complex, so that’s why we need to approach them from multiple different angles.”
Hande Ozdinler, PhD, Associate Professor of Neurology (Neuromuscular Disease), Feinberg School of Medicine
CLP-Feinberg School of Medicine Convergence Workshop
Lightening Talks
The CLP-Feinberg Convergence Workshop, held on September 14, 2022, was the first of a new team science workshop designed to foster innovative research collaborations at Northwestern University that address unmet clinical needs. The Workshop featured lightening talks by CLP faculty researchers and Feinberg physician-scientists, resulting in a vigorous exchange of ideas and several new research collaborations.
Convergence News and Breakthroughs
