Fourteen teams of Columbia faculty have been awarded a Columbia Life Science Accelerator grant to support cutting-edge translational research addressing myriad conditions and disease, including cancer, heart disease, depression, and Alzheimer’s. The recipients of the Life Science Accelerator grants are focused on research and inventions that are on a path to commercialization or the clinic via novel therapeutics discovery or technologies and devices that have the promise to change the way patients are being treated or diagnosed.
The award-winning teams represent diverse interdisciplinary backgrounds, spanning areas of expertise including cancer biology, dental medicine, engineering, microbiology, pathology, psychiatry, and systems biology. The awards are co-funded by a tri-collaboration between the Irving Institute for Clinical and Translational Research through its Translational Therapeutics Accelerator (TRx); the Herbert Irving Comprehensive Cancer Center through its Accelerating Cancer Therapeutics (ACT) program; and the Fu Foundation School of Engineering and Applied Science through its Columbia Biomedical Engineering Technology Accelerator, or BiomedX. The grants, many of which are co-funded across programs, will help the teams fast track their work from the labs to actual application, and along the way, bridging faculty researchers to potential commercial investors, funding resources, and future collaborators.
“These are outstanding scientific teams tackling unmet clinical needs through novel and entrepreneurial approaches,” said Dr. Muredach Reilly, director of the Irving Institute for Clinical and Translational Research. “Our interdisciplinary Life Science Accelerator Program provides teams with expert scientific commercialization guidance and funding to drive their innovations towards market to meet critical clinical gaps for patients.”
The recipients were selected for their potential to translate their research from the lab to commercial market, the scientific novelty and clinical merit of the project, and the feasibility of the proposed work. The teams share a total of $774,000 in pilot funding. TRX, ACT, and BiomedX work closely with Columbia Technology Ventures (CTV), a central hub at the University for technology development initiatives, entrepreneurial activities, and external industry collaborations. CTV helps faculty transfer their inventions or scientific research from academia to the market and established the Columbia Lab-to-Market Accelerator Network to support the expanding landscape of multiple Columbia-affiliated accelerators.
Congratulations to the recipients of the Life Science Accelerator pilot grants (categorized below per funding arm):
Accelerating Cancer Therapeutics (ACT):
“Development of ATAD2 Inhibitors as a Novel Treatment for Metastatic Prostate Cancer”
Lead Investigator: Cory Abate-Shen, PhD, chair of the Department of Pharmacology and professor of pathology and cell biology
Co-Investigator: Donald Landry, MD, chair of the Department of Medicine
Dr. Abate-Shen focuses on the molecular mechanisms of cancer development, with a specialty in prostate cancer research. Prostate cancer is the second-leading cause of cancer deaths in U.S. men, with 33,330 estimated to die in 2020. Whereas localized prostate cancer is successfully managed by active surveillance or local therapy (mainly surgery or radiotherapy) and has five-year survival rates above 99%, metastatic prostate cancer is considered incurable and five-year survival rates drop to approximately 30%. There’s a pressing clinical need to identify the subset of patients at risk of metastasis prostate care and to develop novel therapies in order to improve survival rates. Drs. Abate-Shen and Landry will develop inhibitors of ATAD2, a protein coding gene that can be a bone metastasis driver in prostate cancer patients, and Dr. Abate-Shen will use their proprietary gene-signature to identify high-risk patients that could benefit from this novel therapy.
“NT5C2 Inhibitor to Target Chemotherapy Resistance in Acute Lymphoblastic Leukemia”
Lead Investigator: Adolfo Ferrando, MD, PhD, professor of pediatrics, of pathology and cell biology, and of systems biology (in the Institute for Cancer Genetics)
Co-Investigator: Clara Reglero, PhD, postdoctoral research scientist in the Institute for Cancer Genetics
Dr. Ferrando studies acute lymphoblastic leukemia (ALL), the most common pediatric malignancy, accounting for 30% of all diagnosis, and currently stands as the leading cause of cancer-related death in children. His research at the Institute for Cancer Genetics focuses on determining the cause of relapses in patients with ALL. While several therapeutic protocols have increased the overall survival rates of newly diagnosed pediatric ALL, patients still fail to achieve a complete remission or relapse after intensified chemotherapy. The Ferrando lab has found that NT5C2 genetic mutations are a major cause of resistance to post-remission chemotherapy and are associated with early relapse and progression of ALL. In this project, Dr. Ferrando and his team want to develop specific small molecule NT5C2 inhibitors that, used in combination with 6-MP chemotherapy, would prevent and improve the treatment of relapsed and refractory leukemia patients.
Dr. Han is researching the impact of antibody therapy on familial adenomatous polyposis (FAP), a rare inherited disease in which hundreds of thousands of polyps appear in the intestine. Left untreated, 100% of these patients will develop colorectal cancer by the time they are in their 40s. Currently, the only way to treat FAP is through colectomy, a partial or complete removal of the colon — Dr. Han wants to change that. Besides the risks and complications of surgery, the patients may still develop cancers elsewhere in the body. With Dr. Wang, division chief of digestive and liver diseases, Dr. Han and her lab have already identified a novel oncotarget to treat this inherent disease. Their project will focus on use of antibody therapy to reduce the tumor load to prevent or delay the need of surgery.
“A Multimodal Oral Non-Viral CRISPR-Cas Medical Countermeasure to Enhance Ionizing Radiation Resilience and Survival” (co-funded by CTV)
Lead Investigator: Harris Wang, PhD, associate professor of systems biology and of pathology and cell biology
Dr. Wang and his team are building a therapeutic countermeasure against ionizing radiation. The innovative therapeutic system uses orally administered nanoparticles that deliver CRISPR-Cas radioprotective gene modulators to targeted key sensitive organs to treat acute radiation syndrome (ARS), an unmet medical need in both national defense and cancer treatment. ARS results from high dose exposure of ionizing radiation to the body which causes significant damage, especially to tissues with high turnover rates such as the hematopoietic cells and the gastrointestinal system. Unfortunately, no strategy exists to increase the radiation resilience of gut cells or improve the regeneration of intestinal cell populations. The team’s proposed state-of-the-art technology has the potential to greatly improve radiation resilience and survival to those who suffer from the severely damaging effects of ARS.
Columbia Biomedical Engineering Technology Accelerator (BiomedX):
“Anti-Glycation modification of bioprosthetic heart valve tissues to enhance valve lifespan” (co-funded by TRx)
Lead Investigator: Giovanni Ferrari, PhD, associate professor of surgical sciences (in Surgery)
Co-PIs: Isaac George, MD, associate professor of surgery (in Medicine); Antonio Frasca, PhD, postdoctoral fellow
Bioprosthetic heart valves (BHV), the dominant treatment for heart valve disease, are subject to structural valve degeneration (SVD), which fundamentally limits all clinical BHV to a 15-year average life span. Despite clinical implementation of technologies to address known mechanisms of SVD, valve lifespans have not dramatically improved. The technology being developed by Drs. Ferrari and George, intended for licensing to manufacturers, aims to extend BHV lifespans by chemically modifying BHV tissues to render them inert to physiologic glycation and associated protein incorporation, two interacting, key mechanisms of SVD they recently discovered. By addressing BHV glycation in heart valve replacements, the team hopes to mitigate structural valve degeneration and device failure for all BHV implant recipients, especially younger patients and diabetics.
The Tissue Oracle is a tissue scanning device developed by Drs. Hendon and Hibshoosh that addresses an unmet need to identify which regions of excised breast tissue should undergo histopathological assessment to diagnose breast disease. Their envisioned product deploys optical coherence tomography imaging and artificial intelligence image analysis to achieve the microscopic-level resolution, large field of view, and fast throughput necessary for integration into clinical workflow. The value proposition is that their image-guided sample selection can reduce the number of tissue blocks submitted for histopathology, and the associated cost and workload, by 30-50%. Ultimately this device will help accurately identify regions of interest in breast specimens. The target market are pathologists and administrators seeking greater efficiency for a key step in breast cancer care.
“MRI-Guided personalized TMS”
Lead Investigator: Daniel Javitt, MD, PhD, professor of psychiatry
Co-PI: Paul Sajda, PhD, professor of biomedical engineering, of radiology (in Physics), and of electrical engineering
Transcranial magnetic stimulation (TMS) is an FDA-approved therapy for treatment-resistant depression (TRD). For standard TMS, a magnetic coil is placed over the left frontal head region in order to target the left dorsolateral prefrontal cortex (L-DLPFC), the area of the brain involved in mood control and depression. While somewhat effective, TMS is limited at present by a “one size fits all” approach to estimating the appropriate scalp location across individuals. This project takes advantage of recent advances in brain imaging (atlas based MRI) to precisely localize DLPFC location for each individual prior to stimulation in order to increase targeting precision. The personalized approach developed by Drs. Javitt and Sajda increases effectiveness and reduces cost in comparison to current TMS methods.
“A Growth-Accommodating heart valve for pediatric use” (co-funded by TRx)
Lead Investigator: David Kalfa, MD, PhD, assistant professor of surgery
Co-PI: Jeffrey Kysar, PhD, professor of mechanical engineering
Of the 1.3 million babies born worldwide each year with congenital heart disease, more than 400,000 require implantation of a prosthetic valve during their childhood. This is an extensive process that involves open-heart surgery. Currently these prostheses are of a fixed size. Before reaching adulthood, children must undergo one to four additional valve replacement surgeries to implant a larger valve. Drs. Kysar and Kalfa have developed a polymer prosthesis that accommodates a child’s growth via non-invasive transcatheter balloon dilation. The prosthesis has demonstrated a growth lifespan of more than 10 years. This device is initially intended for pulmonic valve replacement and has the potential to improve outcomes and quality of life for 155,000 children/adolescents per year globally and decrease healthcare costs by reducing open heart reoperations.
“PythonFix: Python-tooth-grasping device for tendon-to-bone repair”
Lead Investigator: Stavros Thomopoulos, PhD, professor of biomechanics
Co-PI: William N, Levine, MD, chair of the Department of Orthopaedic Surgery
Dr. Thomopoulos and his team, alongside Dr. Levine, are working towards transforming the way rotator cuff tears are addressed. Current surgical repair of rotator cuff tears relies on millennia old technology: sutures grasping tendon. Due to stress concentrations at two grasping points the sutures cut through tendon leading to failure of the repair. PythonFix combines a unique mechanical fixation approach with sustained local delivery of biologics. The device consists of a porous base secured at the attachment site and teeth that rise above to grasp tendon. PythonFix fundamentally changes the repair paradigm by distributing load transfer across the entire repair footprint. Initially, they plan to target the repair of massive rotator cuff tears, which show in up to 94% failure rates.
Translational Therapeutics Accelerator (TRx):
“Data-Driven Design of Biologics for the Next Generation of Drug Discovery” (co-funded by CTV and BiomedX)
Lead Investigator: Harmen Bussemaker, PhD, chair of the Department of Biological Sciences
Dr. Bussemaker and his team are addressing an unmet need for improving the speed and quality of biologic drug discovery and a general method for designing and engineering protein-based drugs. Current approaches to biologic drug discovery are either rooted in rational design (based on detailed structural and evolutionary knowledge) or directed evolution (various types of experimental assays, often in the form of iterative schemes). Both strategies come with limitations that make it hard to predict which lead compounds will make it until the end of the full drug development pipeline. In this project, Dr. Bussemaker and his team are attempting to remove the guess work in protein-based drug design and will apply their state-of-the-art computational, data-driven approach to identify relevant molecular metrics of any biopolymer with the most desirable pharmacological properties.
“ReSTORx: A Next-Generation Therapeutic Modality for Protein Stabilization” (co-funded by CTV)
Lead Investigator: Henry Colecraft, PhD, professor of physiology and of cellular biophysics and professor of pharmacology
Dr. Colecraft and his team are developing novel therapeutic modalities targeting the ubiquitin-protease system for the treatment of various ion channelopathies. Cystic Fibrosis is an ion channel disease occurring in ~1:3000 live births and caused by a single loss-of- function mutation in the CFTR Cl-Channel which results in protein processing defects that lead to reduced CFTR on the cell surface. Preliminary data has shown that small molecule targeting of the protein stabilization machinery can lead to improvements in CFTR on the cell surface. Dr. Colecraft has developed a novel platform (ReSTORx) that enables selective recruitment of endogenous deubiquitinases to a specific disease-relevant target. In collaboration with the Organic Chemistry Collaborative Center, this project will validate a small molecule approach for treatments of ion channelopathies.
“Synthetic Design of a Novel Resilience-enhancing Small Molecule Therapeutic Targeting 5-HT4Rs”
Lead Investigator: Christine Ann Denny, PhD, professor of clinical neurobiology (in Psychiatry)
Dr. Denny has developed a novel compound that can be used as a prophylactic for stress-induced psychiatric disorders including major depressive disorder (MDD) and post traumatic stress disorder (PTSD). Exposure to stress is a known risk factor for developing psychiatric disorder, and traditionally, the therapeutic approach has focused on symptom-suppression. However, Dr. Denny’s work has demonstrated that therapeutic compounds may prevent stress-induced behaviors and provide a long lasting self-maintaining protection. Dr. Denny’s findings have been validated in several animal models of stress and clinical studies utilizing existing pharmaceutical compounds; therefore the goals of this study are to develop novel small molecule resilience-enhancers that target the 5-HT4Rs and validate in a mouse model of stress.
“Using Engineered Exosomes for Genome Editing of Lung Cancer Targeting KRAS Mutation” (co-funded by ACT)
Lead Investigator: Fatemeh Momen-Heravi, DDS, PhD, assistant professor of dental medicine
Dr. Momen-Heravi is utilizing the body’s natural transport system as a delivery platform for targeted gene editing in the lung for the treatment of Non-small cell lung cancer (NSCLC). Exosomes are small vesicles shed by all cells in the cellular microenvironment which carry and deliver biomacromolecules. Dr. Momen-Heravi has developed engineered exosomes with the capacity to directly target the KRAS oncogene with CRISPR/Cas technology (CASexo). These CASexos have lung-specific targeting moieties on their surface and are able to carry endogenous active Cas9 proteins and sgRNA targeting the specific KRAS mutation. The goals of this study are to demonstrate that exosome delivery of KRAS-targeted gene editing is effective in animal models of NSCLC.
“Targeting Rare Pediatric Disease Neimann-Pick Type C and Alzheimer’s Disease with Activators of Lecithin” (co-funded by CTV)
Lead Investigator: Laura Beth McIntire, PhD, assistant professor of pathology and cell biology
Through application of a lipid-based high throughput screening platform, Dr. McIntire and her team have identified a key regulator of cholesterol metabolism as a potential target for the treatment of Rare Pediatric Neimann-Pick type C (NPC) and Alzheimer’s Disease. In both Alzheimer’s and NPC, cholesterol metabolism has been established as a critical pathogenic mechanism, with cholesterol sequestration leading to several physiological and behavioral characteristics attributed to neurodegenerative diseases. The team aims to develop small molecule activators that would target lecithin cholesterol acyltransferase (LCAT) activity and restore cholesterol homeostasis in the brain. LCAT has been found to rescue behavioral deficits observed in mice with Alzheimer’s disease upon direct CNS administration. The goal of this study is to develop a brain permeable small molecule activator of LCAT which will facilitate mobilization of cholesterol as a potential prophylactic supplement for Alzheimer’s and novel treatment for NPC.