CGDS Team Publishes Study Supporting Distinct Molecular Mechanisms Underlying ME/CFS

We are excited to share a new paper from the lab and collaborators examining myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) using an individualized, n-of-1 genomic and transcriptomic framework. The study was led by Camille Birch, PhD, Brandon Wilk, Manavalan Gajapathy, Shaurita D. Hutchins, Gurpreet Kaur, Donna M. Brown, Tarun Mamidi, PhD, MS, Kathleen S. Hodgin, Alp Turgut, Jarred Younger, PhD, and Elizabeth A. Worthey.

ME/CFS is a disabling and heterogeneous condition with no validated biomarkers and limited therapeutic options. Clinical variability and unclear pathophysiology have constrained progress in diagnosis and treatment. In this work, we tested whether integrating individual-level genomic and transcriptomic data with deep, participant-informed phenotyping could uncover molecular signatures unique to each patient.

Our findings support the idea that a subset of ME/CFS cases may represent distinct molecular disorders that converge on shared physiological pathways. Importantly, the study suggests that simply increasing cohort size may not be sufficient to resolve causation in a disease defined by rarity, heterogeneity, and molecular complexity. Instead, progress will likely require experimental designs that prioritize individual-level molecular data, rare and common variant effects, and environmental modifiers.

This work motivates a precision medicine framework for ME/CFS that can enable biologically informed stratification, improved trial design, biomarker discovery, and targeted interventions.

We are actively seeking collaborators to extend this approach to much larger and more diverse cohorts. If you or your organization is interested in partnering on future studies, we would welcome the opportunity to connect.

Read the paper at https://link.springer.com/article/10.1186/s12967-025-07586-w.

UAB’s Center for Precision Animal Modeling Receives Continuing NIH Support

The UAB Center for Precision Animal Modeling (CPAM) has received renewed NIH funding (Grant No. 2U54OD030167-06) through 2030 to expand its efforts in modeling human genetic disease. This continuation supports the next phase of the Center’s work (CPAM2.0), enhancing its established framework for variant interpretation, disease modeling, and therapeutic discovery.

The Bioinformatics Section, led by Dr. Liz Worthey, will enhance CPAM’s computational framework through new applications of machine learning, generative AI, and cross-species analysis. This includes expanding Rosalution, which streamlines data integration, variant curation, and collaboration across CPAM teams. The renewed funding underscores CPAM’s role in translating genomic findings into actionable insights that accelerate diagnosis and treatment for rare diseases.

Congratulations to Dr. Tarun Mamidi!

We are thrilled to celebrate Dr. Tarun Mamidi, who graduated from UAB on Saturday, December 14th.

Dr. Mamidi defended his dissertation, “Improving Molecular Diagnosis Success Rates and Prognosis Prediction for Patients With Rare Diseases,” in June 2024.

He will begin his new role as a Bioinformatics Scientist at Children’s Mercy while continuing as a consultant in our lab.

We wish you continued success in your career, Tarun!

CGDS Team Publishes Largest Genomic Study to Date That Reveals RAS Pathway Involvement in JGCTs

Ten juxtaglomerular cell tumors (JGCTs) from nine institutions were analyzed using immunohistochemistry and whole exome sequencing. The study highlights significant morphologic variability, with tumors mimicking other renal neoplasms. Although three tumors exhibited concerning histologic features, patient outcomes were favorable, suggesting that morphology alone is not predictive of clinical behavior.

Genomic analysis identified activating variants in RAS GTPases without other recurrent alterations. These findings implicate the MAPK–RAS pathway in JGCT development and represent the largest JGCT series characterized by whole exome sequencing to date.

Read the full publication in Modern Pathology: Molecular Characterization of Juxtaglomerular Cell Tumors: Evidence of Alterations in MAPK-RAS Pathway.

CGDS and Rosalution Featured in NIH Research Highlights

We’re excited to share that our lab’s work was featured in the NIH Research Highlights post on the University of Alabama at Birmingham’s (UAB) Center for Precision Animal Modeling (C-PAM). This recognition underscores our contributions to advancing precision disease modeling, a field at the forefront of personalized medicine.

C-PAM is one of three U54 centers established under the NIH Precision Disease Modeling Initiative, focused on creating advanced animal models for precision therapies targeting complex disorders like ciliopathies and Roberts syndrome. Our tool, Rosalution, plays a key role in these efforts, helping link unique human genomic variants to disease with high-throughput, cost-effective pipelines.

This recognition highlights our lab’s commitment to developing innovative tools that enhance our understanding of disease mechanisms and empower clinicians and researchers.

Read more about the initiative and C-PAM’s work here.