Roy and Diana Vagelos Precision Medicine Pilot Awards 

Pilot Awards Granted to Five Teams to Advance Precision Medicine Research

Jointly awarded by the Columbia Precision Medicine Initiative (CPMI), the Herbert Irving Comprehensive Cancer Center (HICCC), and the Irving Institute for Clinical and Translational Research (Irving Institute), the Precision Medicine Pilot Awards underscore Columbia’s commitment to supporting research targeting the promise of precision medicine, across multiple diseases. The five teams will each receive $100,000 in funding for one year.

The Roy and Diana Vagelos Precision Medicine Pilot Awards are a cornerstone of the CPMI mission: to establish world class academic research centers of excellence to build precision medicine as a basic and applied science at Columbia. Seeding basic research in precision medicine with these awards is an efficient way of converting this money to external research grants and we look forward to this return on investment in due course.

The three winning Vagelos proposals reflect the high standard and the broad base of precision medicine basic science research being conducted and conceived at Columbia. They cover research into the role of the vaginal microbiome in premature births; the skin disease hidradenitis suppurativa; and a high-throughput screening strategy to identify splicing-regulatory elements for any gene.

Further details of the winning Vagelos applications are below, in addition to the Irving Institute and HICCC winners.

Roy and Diana Vagelos Precision Medicine Pilot Awards:

“Mechanistic Investigation of the Vaginal Microbiome in Different Manifestations of Spontaneous Preterm Birth”
Lead Investigator: Tal Korem, PhD; Co-PIs: Anne-Catrin Uhleman, MD, PhD; George Gallos, MD; Joy-Sarah Vink, MD

Spontaneous preterm birth (sPTB) is a leading cause of neonatal morbidity and mortality. The vaginal microbiome is associated with sPTB, but the underlying mechanisms are largely unknown. This stems from low taxonomic resolution attainable from 16S rRNA amplicon sequencing, and from the oversimplified clinical profiling of sPTB, which ignores the heterogeneity in its pathophysiology. Dr. Korem and his lab will optimize methods for bacterial DNA extraction and perform metagenomic sequencing of vaginal microbiome samples from a deeply-phenotyped cohort of pregnant women. They will study host-microbiome interactions in the context of sPTB and its underlying etiologies, using microbiome analysis methods which raise mechanistic insights regarding microbial growth rates, genomic variation, and predicted metabolite production. They intend to validate promising hypotheses in vitro and by metabolomic analysis of a subset of samples, and their aim is that this research will lead to novel insights regarding the involvement of the microbiome in different manifestations of sPTB, addressing a critical gap in the field.

“Deciphering Monogenic and Polygenic Etiologies of a Longitudinal Multi-Ethnic Hidradenitis Suppurativa Cohort”
Lead Investigator: Lynn Petukhova, PhD; Co-PI: Suzanne Leal, PhD

Drs. Petukhova and Leal are investigating the chronic skin disease, hidradenitis suppurativa (HS), aiming to find better ways to manage and hopefully prevent it. HS, which typically appears after puberty, causes painful lumps to form deep within the skin. The condition can persist for many years and get worse over time. There is currently a lack of therapies and understanding of HS, causing patients’ needs to remain unmet. The researchers believe that HS has a genetic architecture that is similar to other chronic inflammatory diseases. They will be studying a multi-ethnic group of participants with HS, with a goal of garnering new knowledge about the biological drivers of disease.

“Unbiased Screen of Proximal and Distal Splicing Regulatory Elements Towards Drug Discovery.”
 Lead Investigator: Chaolin Zhang, PhD; Co-PI: Samuel Sternberg, PhD

Numerous Mendelian diseases are caused by mutations that disrupt individual genes and could potentially be treated by modulating gene expression to restore normal protein production. A level of molecular regulation called alternative splicing occurs ubiquitously in human genes and frequently generates a combination of RNA isoforms that code for proteins or are noncoding. Modulation of alternative splicing using synthetic genetic strings called antisense oligonucleotides (ASOs) to target splicing regulatory elements has recently emerged as a powerful means of increasing gene expression levels. For example, SPINRAZA is an FDA-approved ASO drug that targets the SMN2 gene to treat spinal muscular atrophy. A critical challenge, however, is pinpointing the most effective regulatory RNA elements that can be targeted to modulate splicing. Drs. Zhang and Sternberg are proposing a high-throughput screening strategy to do just that—to exhaustively identify splicing-regulatory elements for any gene.

Herbert Irving Comprehensive Cancer Center Award:

"Biological and Therapuetic Relevance of Exosomes in Uveal Melanoma"
Lead Investigator: Richard Carvajal, MD; Co-PIs: Alex Rai, MD; Grazia Ambrosini, PhD

Dr. Carvajal, alongside Drs. Rai and Ambrosini, are working towards identifying a treatment strategy that can prevent the development of metastatic uveal melanoma (UM). UM is a rare melanoma that is distinct from those that start in the pigment producing cells of the skin. Recent analyses of UM patients have shown an increase of proteins contained with exosomes, small vesicles or blisters released from the cell. Cancer-derived exosomes contribute to cancer development and progression, making them both a potential indicator of disease and an opportunity for intervention. The researchers will further assess the role of the exosomes in UM disease progression. The end goal is to identify one or more lead treatment strategies to prevent the development of metastatic disease and devise a clinical trial for patients at high risk for disease recurrence.

Irving Institute for Clinical and Translational Research Award:

“A microRNA Approach to Identify Renal Osteodystrophy Sub-Type”

 Lead Investigator: Thomas Nickolas, MD, MS; Co-PIs: Stavroula Kousteni, PhD; Krzysztof Kiryluk, MD, MS

Together, with his collaborators Drs. Kousteni and Kiryluk, Dr. Nickolas is tackling renal osteodystrophy (ROD), a disorder that weakens the skeleton, resulting in bone loss, fractures, and cardiovascular complications. ROD can be classified based on changes in bone turnover rates as high-turnover ROD (markedly elevated) or low-turnover ROD (markedly suppressed. Currently, treatment of ROD focuses on stopping high-turnover ROD, while also avoiding the development of low-turnover ROD that can occur through excessive use of these treatments. There currently is a strong need for a better system of diagnosing bone turnover rate in patients in order to better manage disease treatment. The team believes circulating fragments of cellular RNA called microRNAs (miRNAs) can assess turnover types in ROD. They are looking to identify miRNA profiles in order to test them as biomarkers of ROD turnover-type, positively impacting the diagnosis and management of ROD.