# Systems biology frameworks to unravel mechanisms driving complex disorders

> **NIH NIH K25** · CASE WESTERN RESERVE UNIVERSITY · 2021 · $171,720

## Abstract

Project Summary/Abstract
This application proposes a training program to integrate the PI, Dr. Varadan's previous research efforts in
informatics and machine learning into investigations pertaining to the etiology and progression of Barrett's
Esophagus, a gastrointestinal disorder of significant public health interest. Much of Dr. Varadan's previous
research has involved developing intelligent algorithms and informatics approaches to decode the
interconnections within complex biological systems, with only a basic understanding of the clinical needs and
complexities involved in translational research. The proposed project would provide a broad and in-depth
mentored experience focused on clinical and biological aspects of Barrett's Esophagus, as well as added
knowledge in the use of preclinical model systems to investigate biological mechanisms. The overall goal is to
expand the PI's experience and training in the design and conduct of translational studies focused on
gastrointestinal (GI) diseases. This objective will be achieved through a combination of didactic and research
activities conducted under an exceptional mentoring team of translational researchers at Case Western
Reserve University, spanning achievements across clinical management of GI disorders, molecular genetics
and inflammatory processes associated with diseases of the gut. Accordingly, this proposal leverages Dr.
Varadan's computational background to address an urgent and unmet need within the biomedical research
community to develop reliable analytic approaches that can quantify signaling network activities in individual
biological samples by integrating multi-omics measurements. We recently conceived a systems biology
computational framework, InFlo, which integrates molecular profiling data to decode the functional states of
cellular/molecular processes underpinning complex human diseases. Barrett's esophagus is one such complex
disease gaining increasing importance to public health, as it is the known precursor to the deadly cancer,
esophageal adenocarcinoma. Given that the mechanisms underlying the etiology and pathogenesis of Barrett's
Esophagus remain elusive, a major objective of this proposal is to employ the InFlo framework combined
molecular profiles derived from primary tissue cohorts, in vitro and in vivo model systems to establish the
molecular roadmap of BE pathogenesis and disease recurrence, thus elucidating unifying mechanisms
underlying this disease. This systems biology approach would enable the development of evidence-based,
diagnostic/prognostic biomarkers for Barrett's esophagus and inform preventive strategies within at-risk
populations.

## Key facts

- **NIH application ID:** 10086862
- **Project number:** 5K25DK115904-03
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** Vinay Varadan
- **Activity code:** K25 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $171,720
- **Award type:** 5
- **Project period:** 2019-04-01 → 2021-05-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10086862

## Citation

> US National Institutes of Health, RePORTER application 10086862, Systems biology frameworks to unravel mechanisms driving complex disorders (5K25DK115904-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10086862. Licensed CC0.

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