Twelve winning research teams led by Columbia University faculty, across diverse disciplines, have received a Columbia Life Science Accelerator pilot grant for their creative and inventive lab-to-market projects. Award recipients, representing areas of expertise from bioengineering to mechanical engineering and genetics to systems biology, are each focusing on research or inventions that are on a path to commercialization or the clinic via novel therapeutics discovery or technologies that aim to change the way patients are being treated or diagnosed.
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 this year share a total of $780,500 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, or BiomedX. The three groups work closely with Columbia Technology Ventures (CTV), a central hub at the University for technology development initiatives, entrepreneurial activities, and external industry collaborations, and by the Columbia Lab-to-Market Accelerator Network, a framework to successfully develop, launch, and execute initiatives to help commercialize academic research.
Congratulations to the recipients of the 2021 Life Science Accelerator pilot grants (categorized per funding arm):
Accelerating Cancer Therapeutics (ACT)
"NAMPT Inhibitors for Diffuse Large B-Cell Lymphoma"
Investigators: Riccardo Dalla-Favera, PhD, professor of clinical medicine, of pathology and cell biology, and of microbiology and immunology of the Institute for Cancer Genetics; Claudio Scuoppo, PhD, instructor at the Institute for Cancer Genetics
Diffuse Large B-Cell Lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma worldwide with some 50,000 new cases per year in the U.S. Approximately 40% of patients do not respond to first-line therapies, while the response rates of second-line therapies, new molecularly-targeted drugs, and cell-based therapies, remain limited. By screening drugs that are approved or in advanced clinical development, Drs. Dalla-Favera and Scuoppo have identified inhibitors of Nicotinamide Phosphoribosyl Transferase (NAMPT), the rate-limiting enzyme of the Nicotinamide Adenine Dinucleotide (NAD) Salvage pathway, as the top drug compounds showing potent activity against a major genetically characterized subtype of DLBCL that accounts for about 65% of total cases. Treatment in mice models showed that systemic NAMPT inhibition is active against DLBCL and is not toxic. The team has developed multiple assays to characterize the on-target activity and the relative potency of the currently available NAMPT inhibitors, which have not been previously tested against DLBCL and are also of limited potency. Based on these data, the team plans to generate and validate new potent NAMPT inhibitors aimed at treating DLBCL.
"Mirin-based Inhibitors of the Mre11 Nuclease: targeting the DNA damage response for Cancer Therapy"
Investigators: Jean Gautier, PhD, professor of genetics and development in the Institute for Cancer Genetics; Brent Stockwell, PhD, professor of chemistry
DNA repair mechanisms are critical in suppressing tumors. Defects in DNA repair occur in subsets of difficult-to-treat breast, prostate, and pancreatic cancers. These tumors with unstable genomes have critically high death rates and current treatment options are not adequate. A team, led by Drs. Gautier and Stockwell, is focusing on the development of inhibitors of a DNA repair enzyme called Mre11 nuclease, following their research discovery and characterization of mirin, a highly specific inhibitor of Mre11 and the first inhibitor of a DNA repair nuclease. Mre11 also acts to repair lesions generated by DNA topoisomerase inhibitors and gemcitabine, both widely used chemotherapy drugs, and Mirin-based Mre11 inhibitors also have the potential to increase the efficacy of these treatments. Mirin and derivatives have therefore a wide range of potential applications as cytotoxic drugs for tumors with mutations in DNA repair pathways, tumors with heavy mutation burden, and/or in combination with DNA damaging chemotherapies.
Columbia Biomedical Engineering Technology Accelerator (BiomedX)
"SONO-PATCH: The World's First Wearable Imaging Device"
Investigators: David Kessler, MD, M.Sc, associate professor of pediatrics (in emergency medicine); Ken Shephard, PhD, professor of electrical engineering and of biomedical engineering
Critically ill patients are often subject to continuous physiologic monitoring and repeated imaging tests to manage their care. Wearable ultrasound devices provide non-invasive, continuous physiologic monitoring as well as medical diagnostics. SONO-PATCH is a wearable 2D array in the form of a conformational patch probe that can be placed externally on the body's surface to allow for continuous sonographic visualization and hands-free operation.
"AutoDetect: Diagnostic Tool for Autoimmune Myocarditis"
Investigators: Gordana Vunjak-Novakovic, PhD, professor of biomedical engineering and of medical sciences; Robert Winchester, MD, professor of medicine and of pathology and cell biology, and pediatrics; Laura Geraldino-Pardilla, MD, assistant professor of medicine
There are 10.5 million Americans who are at elevated risk for autoimmune myocarditis and ultimately heart failure. The onset of heart failure can be prevented by diagnosing and treating early-stage myocarditis, however, current diagnostics are inaccurate, unreliable, or inaccessible due to cost. AutoDetect is developing a highly sensitive and specific diagnostic tool that can identify early-stage myocarditis, which would otherwise go undetected. AutoDetect could aid in risk stratification and facilitate etiology-based therapies.
"A living yeast biosensor for diagnostic applications"
Investigators: Virginia Cornish, PhD, professor of chemistry; Alastair Ager, PhD, adjunct professor of population and family health; and Thomas Briese, PhD, associate professor of epidemiology
There is an unmet need for low-cost, sensitive, specific, simple, and rapid diagnostics to efficiently identify viral infections, such as SARS-CoV-2, that can be performed at home and at scale. Current at-home solutions are cost-prohibitive: the At-Home Antigen Lateral Flow Assays diagnostics remains >$10/test because of manufacturing, shipping, and storing antibodies, while LAMP-based diagnostics offer molecular accuracy but cost >$50/test for routine testing. The biosensor is a superior diagnostic created by engineering live yeast using synthetic biology. It eliminates the need for expensive equipment and additional reagents by engineering yeast to produce red pigment in response to a given pathogen. Dried yeast can be globally distributed as an inexpensive, safe, simple, and reliable alternative to other diagnostics for routine testing.
"OnXpansion: Automated, targeted expansion of patient tumor samples for clinical biomarker analysis and personalized treatment" (Co-funded by ACT)
Investigators: Anjali Saqi, MD, MBA, professor of pathology and cell biology; Keith Yeager, M Eng, research engineer
At least 40% of biopsies may be inadequate (and thus must be repeated), delaying tumor analysis and personalized cancer care. Currently, increasing biopsy sample size would require changing from a minimally invasive, outpatient
procedure to a surgical procedure, causing increased costs, resource utilization, and morbidity. The current practices to address these shortcomings-repeat biopsy, liquid biopsy, and patient-derived xenografts-all have their own disadvantages. OnXpansion addresses this issues by providing a method and device for expanding scant patient samples into clinically useful quantities for diagnostic biomarker testing for personalized cancer treatments.
Translational Therapeutics Accelerator (TRx)
"Treatment for Working Memory Deficits in Neurodevelopmental Disorders"
Investigators: Alex Dranovsky, MD, PhD, associate professor of psychiatry; Amy Margolis, PhD, associate professor of psychiatry
People with neurodevelopmental disorders, such as attention deficit hyperactivity disorder (ADHD), non-verbal learning disability (NVLD), and others, often suffer from working memory impairments. Although these deficits account for much of the morbidity in these patient populations, current treatments for ADHD and other neurodevelopment disorders do not target or remediate working memory deficits. Other disorders such as NVLD currently have no approved treatments at all. Dr. Dranovsky and his team have established a mouse model where changes in a single circuit lead to profound spatial working memory deficits and have demonstrated that these deficits can be alleviated by targeting components of the circuit. Dr. Margolis has found that patients with NVLD and working memory impairments exhibit fMRI changes in the same circuit. The team is using these findings to actively develop pharmacological interventions for working memory impairments that would improve daily life for patients with neurodevelopmental disorders.
"CultivageBio: Vaginal Probiotic Cocktail" (co-funded by BiomedX)
Investigators: Harris Wang, PhD, assistant professor of systems biology; Mary Rosser, MD, PhD, assistant professor of obstetrics and gynecology
Vaginal microbiome (VM) imbalances are a risk factor and pathological feature of various reproductive conditions (e.g. pre-eclampsia, preterm birth, and infertility). The most common resulting disease is bacterial vaginosis (BV), an overgrowth of anaerobic pathogens that can cause pain, discomfort and excess malodorous vaginal discharge. BV affects 30% of women worldwide, with higher rates in non-white populations. Typical treatments, such as antibiotics, indiscriminately wipe out both pathogens and "healthy" bacteria, potentially leaving patients susceptible to immune system compromises. Probiotics are a promising avenue to treat BV, however, they are limited in efficacy, likely because existing probiotic supplements are missing a key factor: community-level microbial interactions. The team is developing a diverse, stable VM cocktail that can be used to treat VM dysbiosis.
"Development of enhanced CAR T regs for targeted induction of immune tolerance" (co-funded by BiomedX)
Investigators: Mohsen Maharlooei, PhD, associate research scientist; Megan Sykes, MD, professor of medicine and of microbiology and immunology, and surgical sciences (in surgery)
One of the major challenges in healthcare today is controlling immune responses in the settings of autoimmunity and transplantation. With the steady rise in the rate of autoimmune diseases, and continuing growth of waiting lists for transplantations, there is a need for a safer and more effective immunosuppressive therapy. Regulatory T cell (Treg) therapy is a promising method to induce immune tolerance and control undesired immune responses. Antigen-specific Tregs, including genetically engineered chimeric antigen receptor (CAR) Tregs, are superior to polyclonal (non-specific) Tregs. However, there are major concerns regarding the potential for CAR Tregs to convert to other T cell types that could be detrimental and the negative effect of conditioning regimens given to patients on the therapeutic CAR Tregs. The team is proposing to improve the efficacy of CAR Treg therapy through implementing strategies aimed at making CAR Tregs resistant to conversion and conditioning toxicity and also enhancing their immunosuppressive capabilities.
"Pro-CARs Probiotic-guided CAR-T cells for universal solid tumor targeting" (Co-funded by ACT)
Investigators: Tal Danino, PhD, associate professor of biomedical engineering; Nicholas Arpaia, PhD, assistant professor of microbiology and immunology
The powerful union of synthetic biology and cancer immunotherapy has driven a new age of intelligent, tumor-antigen targeting therapies like chimeric antigen receptor (CAR)-T cells. While CAR-T cell therapy has demonstrated remarkable efficacy against blood cancers, the difficulty of defining safe tumor antigens on heterogenous solid tumors has greatly narrowed its success for difficult-to-target indications. Microbes seeking low oxygen, low pH, and immunosuppressive environments - hallmarks of solid tumors - selectively colonize the necrotic tumor core irrespective of tumor antigens, and have thus emerged as novel programmable therapeutics. Bridging these observations, Drs. Danino and Arpaia have developed a platform of probiotic-guided CAR-T cells (ProCARs), in which T cells are engineered to sense and respond to synthetic antigens that are controlled and released by tumor-homing probiotic bacteria. With this platform they have expanded potential applications of both bacteria and CAR-T cell therapy to allow improved treatment for a wide range of solid tumors.
"Leveraging Single-Cell Technologies with Advanced Machine Learning and Gene Network-Based Predictive Algorithms to Identify Novel Targets Driving Radiation Therapy Resistance" (Co-funded by ACT)
Investigators: Catherine Spina, MD, assistant professor of radiation oncology; Andrea Califano, Dr, chair and professor of systems biology
The National Cancer Institute estimates that 39.5% of people will be diagnosed with cancer at some point in their lifetime. More than half of all cancer patients are treated with radiotherapy as part of their cancer-directed therapy. Despite the curative intent of definitive radiation, efficacy is not guaranteed with progression of disease often driving fatal outcomes. In addition to eliminating tumor cells by irreparable DNA damage, emerging data has shown that radiation therapy promotes a therapeutically meaningful anti-tumor adaptive immune response. However, this is countered by immunosuppressive changes in the tumor microenvironment that drive therapy resistance. This research team's goal is to leverage their unique single-cell proteogenomic dataset and advanced machine learning and regulatory gene network-based predictive algorithms to identify novel targets and lead compounds for combination with radiation to mitigate acquired radioresistance.
"SARS-CoV-2 Envelope as a new therapeutic target for COVID-19"
Investigators: Masayuki Yazawa, PhD, assistant professor of rehabilitation and regenerative medicine and of molecular pharmacology and therapeutics; David Ho, MD, professor of medicine and of microbiology and immunology
COVID-19 (SARS-CoV-2) pandemic affected approximately 56 million people in the world in 2020. While vaccines against COVID-19 are now approved for use, there are limited treatment options for patients suffering from the virus as well as novel mutants. To address the growing concern of viral mutations, the labs of Drs. Yazawa and Ho are developing therapeutics that target the SARS-CoV-2 envelope (E) protein, which form ion channels important for virus function and appear much less susceptible to mutations compared to other SARS-CoV-2 proteins. To accomplish this goal, the researchers will use high-throughput bioluminescence reporter assay and live cell imaging to examine the effect of synthetic peptide and antibody candidates on SARS-CoV-2 E channel activities using mammalian heterologous expression systems. Top candidates will be assessed for efficacy on live SARS-CoV-2 viruses.
