Lab-to-Market Innovations Win New Funding
Ten research teams led by Columbia University faculty, across multiple disciplines, have received a Columbia Life Science Accelerator Pilot Grant for their out-of-the-box lab-to-market projects. Researchers are addressing a diverse array of problems in several disciplines, from engineering and medicine to bioimaging and oncology. The winning projects focus on research or inventions that are on a path to commercialization and have real-world applications in the clinic that can impact patient care and diagnosis.
The awardees were selected for their potential to translate their research from the lab to commercial market, and stood out for their truly novel scientific solution and clinical merit. The teams this year share a total of $747,000 in pilot funding.
The annual Life Science Accelerator pilots are co-funded by 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 Columbia Engineering through its Biomedical Engineering Technology Accelerator (BiomedX). The three groups work closely with Columbia Technology Ventures (CTV), a central office at Columbia for technology development initiatives, entrepreneurial activities and industry collaborations, and the Columbia Lab-to-Market Accelerator Network, a framework to successfully develop, launch and execute initiatives to help commercialize academic research.
Congratulations to the 2022 Life Science Accelerator Pilot Grant Awardees (categorized per funding arm):
Accelerating Cancer Therapeutics (ACT)
SAAMIZUMAB: A monoclonal antibody therapy to target the niche and prevent relapse in hematological myeloid malignancies
Lead PI: Marta Galan Diez, PhD, adjunct associate research scientist in the Department of Physiology and Cellular Biophysics and staff scientist at Regeneron Pharmaceuticals Inc.
Co-PI: Stavroula Kousteni, PhD, Edward P. Evans Professor of Myelodysplastic Syndromes Research (in Physiology and Cellular Biophysics and in the Herbert Irving Comprehensive Cancer Center)
Low survival and high relapse rates in acute myeloid leukemia (AML), one of the deadliest blood cancers, remain a significant problem, highlighting the need for novel therapies. The bone marrow niche has been recognized as crucial in the pathogenesis and chemoresistance of blood cancers. In this project, the researchers take a closer look at targeting a novel MDS- and AML-niche crosstalk in bone responsible for perpetuating disease progression. This novel treatment approach has already proven to work in leukemic mouse models and in patient-derived xenograft models that showed when this niche is interrupted by pharmacological targeting or gene editing, AML progression is either hampered or halted entirely. The aim is that this treatment approach could be broadly applicable as a standalone intervention, or in combination with chemotherapy, preventing the spread and relapse of MDS (a pre-leukemic state) and/or AML.
The Annihilator: A first-in-class small molecule treatment for metastatic colorectal cancer
Lead PI: Joseph Garcia, MD professor of medicine
Co-PI: Charles Karan, PhD, scientific director of High-Throughput Screening Facility at Columbia Genome Center
Advanced (metastatic) cancers originating from solid tumors often have limited treatment options and poor long-term survival. Simultaneous targeting of multiple components in an essential signaling pathway may result in more effective treatments for these advanced cancers. The researchers aim to identify first-in-class, drug-like small molecules that selectively target the dual-functional protein Acss2 via an unconventional method. Therapy directed against Acss2, a cytosolic metabolic enzyme and nuclear signal transducer, may reduce or stop growth and metastasis of solid tumors including advanced stages of colorectal cancer.
Targeting VRK2 to enhance cancer immunotherapy
Lead PI: Adam Mor, MD, Herbert and Florence Irving Associate Professor of Rheumatology (in Medicine)
Co-PI: Shalom Lerrer, PhD, postdoctoral research scientist in the Department of Medicine
Cancer immunotherapies are a powerful and emergent therapy, both for their durable clinical responses and applicability to a wide variety of tumors. Despite the success of a particular immunotherapy, anti-PD-1/PD-L1 antibodies, that shuts down a pathway signaling T-cells to turn “off”, most patients do not respond to PD-1 blockade, and many patients experience immune-related side effects from the treatment. Dr. Mor and collaborators have identified the T-cell kinase enzyme, VRK2, as instrumental in supporting the inhibitory T-cell functions of PD-1. To improve anti-PD-1/PD-L1 immunotherapies and stop tumor growth in patients, the team is developing Fortex, an oral small-molecule drug to specifically target VRK2 in the treatment of non-small cell lung cancer.
Columbia Biomedical Engineering Technology Accelerator (BiomedX):
UltraNav: Novel Focused Ultrasound Device for Drug-Free Treatment of Alzheimer’s Disease (co-funded by TRx)
Lead PI: Elisa Konofagou, PhD, Robert and Margaret Hariri Professor of Biomedical Engineering and professor of radiology (in Physics)
Co-PI: Lawrence S. Honig, MD, PhD, professor of neurology
Alzheimer’s disease affects over 6 million people in the United States alone, with devastating economic and healthcare consequences. Abnormal aggregation of beta-amyloid and tau protein is a hallmark feature of Alzheimer’s disease, and clearance of protein aggregates remains a major focus for Alzheimer’s therapies. The team of Drs. Konofagou and Honig developed UltraNav (ultrasound + navigation) which transiently opens the blood brain barrier in a focused region and stimulates an immune response to clear beta-amyloid plaque and tau. Clinical safety and preliminary efficacy have been demonstrated in pre-clinical and early-stage clinical studies. Funding from BiomedX and TRx will enable investigation of tau pathology in patients receiving treatment with UltraNav.
Artificial Intelligence-Powered Dental Disease Detection
Lead PI: Helen H. Lu, PhD, Percy K. and Vida L.W. Hudson Professor of Biomedical Engineering
Co-PIs: Sunil Wadhwa, DDS, Leuman W. Waugh Associate Professor of Orthodontic Dental Medicine; Michael T. Yin, MD, associate professor of medicine in the Division of Infectious Diseases
Periodontal disease, characterized by progressive bone loss, and caries (cavities) are the two most common dental conditions, impacting nearly 50% of U.S. adults. Diagnosis and monitoring of periodontal disease and caries currently rely on qualitative assessment of dental radiographs. The team of Drs. Helen Lu, Sunil Wadhwa, and Michael T. Yin developed an artificial intelligence (AI) algorithm for rapid and accurate assessment of dental radiographs for detection and monitoring of bone loss. This innovative approach to radiographic assessment could improve diagnostic accuracy and throughput, enable longitudinal tracking of disease state, and inform treatment strategies in patients with periodontal disease and caries.
NeuroFlex: Wireless, High-Resolution Neural Interface for Drug-Resistant Epilepsy (Co-funded by TRx)
Lead PI: Brett Youngerman, MD, MS, assistant professor of neurological surgery
Co-PI: Kenneth Shepard, PhD, Lau Family Professor of Electrical Engineering and professor of biomedical engineering
Patients with epilepsy suffer from seizures, cognitive decline, and decreased life expectancy. Approximately one third of patients with epilepsy are drug-resistant and face uncontrolled seizures. While surgical intervention can mitigate symptoms and improve quality of life, surgical treatment of epilepsy is largely underutilized due to its invasiveness, multi-step complexity, and high cost. To address the need for a lower-cost, single-step intervention to treat drug resistant epilepsy, the team of Drs. Youngerman and Shepard developed a flexible, wireless, high-resolution neural interface for diagnostic seizure monitoring and therapeutic neuromodulation. Following placement, this device improves real-time neural mapping accuracy and supports therapeutic efficacy without the need for additional surgeries.
Translational Therapeutics Accelerator (TRx)
Bain Syndrome: A Gene Targeted Approach for HNRNPH2-Related Neurodevelopmental Disorder
Lead PI: Jennifer Bain, MD, PhD, assistant professor of neurology and of pediatrics
Co-PI: Christopher Ricupero, PhD, associate research scientist in dental medicine
Understanding rare genetic disorders and potential interventions for neurodevelopmental disorders is a significant healthcare challenge. The team, led by Drs. Bain and Ricupero, will build on their earlier work identifying a rare neurodevelopmental disorder, “Bain syndrome,” caused by an X-linked gene, HNRNPH2, that is associated with developmental delays, intellectual disability, motor and language impairments, epilepsy, and autism. There is no cure and nearly all affected individuals are nonverbal and nonambulatory, requiring lifelong care. The team is modeling the disorder and developing an innovative gene therapy to neutralize or correct the disease gene variants, using antisense oligonucleotides (ASOs) and base editors, as well as identifying essential biomarker endpoints necessary for clinical trials. The ultimate goal is to develop a treatment that will address the root cause of neurological symptoms in Bain Syndrome and improve the patients’ quality of life.
Bio-Microbur for Oral Delivery of Biologics (co-funded by ACT and BiomedX)
Lead PI: Kam Leong, PhD, Samuel Y. Sheng Professor of Biomedical Engineering and professor of systems biology
Most patients prefer to take oral medications over injections, which are more burdensome and expensive. However, many therapies, such as insulin, must be delivered via injection because if taken orally they get degraded by the digestive system and are not well absorbed. To address these problems, Dr. Leong and team have developed a tiny swallowable device, a “bio-microbur,” inspired by sticky fruit burs that adhere to animal furs and clothing. The bio-microbur will protect labile drugs, prolong their retention, and enhance their absorption by the digestive system. After the bio-microbur sticks to the intestinal wall, the nanospikes and the coatings will biodegrade and release drugs or nanoparticles that carry drugs across intestine walls for safe and efficient delivery of critical therapies. The team will test a proof-of-concept for the device to ultimately establish a new platform technology for the efficient oral delivery of biologics.
Calcardia – Precision Treatment for Heart Failure
Lead PI: Steven Marx, MD, Herbert and Florence Irving Professor of Cardiology (in Medicine) and professor of molecular pharmacology and therapeutics
Co PI: Manu Ben-Johny, PhD, assistant professor of physiology and cellular biophysics
When the heart cannot pump enough blood to meet the body’s metabolic needs, people experience heart failure and are at risk for lethal arrhythmias. Approximately 25,000 end-stage heart failure patients in the United States require intravenous medications called inotropes that keep them alive making the heart contract and pump more blood to the body. Unfortunately, these medications have dangerous side effects, including tachycardia and low blood pressure. The team, led by Drs. Marx and Ben-Johny, aims to develop inotropes that improve cardiac function without these dangerous side effects. They discovered a novel mechanism for how inotropes increase the strength of cardiac contractions—by preventing inhibition of the voltage-gated calcium channels in heart—and developed a patented, high-throughput screening program to identify compounds that mimic this mechanism. The most promising compounds will be used to develop a heart-specific treatment with fewer dangerous side effects and the potential for a transformative outpatient oral treatment.
Prime editing: Novel CRISPR-based Therapy for CRB1-Linked Inherited Retinal Dystrophies
Lead PI: Stephen H. Tsang, MD, PhD, Laszlo T. Bito Professor of Ophthalmology and professor of pathology and cell biology
Co-PI: Peter M.J. Quinn, PhD, associate research scientist in ophthalmology
Inherited retinal dystrophies, diseases that damage the eye’s retina, are a leading cause of blindness. Drs. Quinn and Tsang and their team will target inherited retinal dystrophies (IRDs) caused by the crumbs homologue-1 (CRB1) gene, which affects approximately 80,000 patients worldwide and has no treatments currently available. They aim to develop an effective genome editing strategy that will correct the genetic mutations and prevent disease progression. The team will use prime editing, a novel CRISPR-based gene editing technology, to treat mutations in this gene, using CRB1 patient induced pluripotent stem cell (iPSC) and patient iPSC-derived retinal organoids to assess the potential of gene editing as a treatment for patients suffering from CRB1-associated IRDs.