NIH provides $9.3 million grant to create new Center for Precision Animal Modeling at UAB

A new Center for Precision Animal Modeling, or C-PAM, has been created at the University of Alabama at Birmingham, supported by a five-year, $9.3 million grant from the National Institutes of Health's Office of Research Infrastructure Programs.

The UAB C-PAM is one of only three centers in the United States funded through a highly competitive NIH program to create national centers for "precision disease modeling." UAB submitted a 15-member team proposal led by Brad Yoder, Ph.D., chair of the UAB Department of Cell, Developmental and Integrative Biology, and Matt Might, Ph.D., professor in the UAB Department of Medicine and director of the Hugh Kaul Precision Medicine Institute.

Yoder and Might say the new center is a recognition of UAB's national reputation for leadership in both precision medicine and model organism research.

Precision disease modeling involves creation of patient-specific disease models -- often using yeast, worms, fruit flies, zebrafish, frogs, mice or rats -- that mimic the molecular character of a condition present in a patient. For example, if a patient has a disease caused by a sequence variant leading to the dysfunction of a gene, then C-PAM will create an animal model with this same variant. Studying the effect that the variant has in the model makes it possible to do science that is not possible in the human patient.

Computational capabilities at UAB -- including advanced data science and artificial intelligence -- will help predict possible treatments that can be tested in the models. Therapies that help treat the model would then become candidates for treatment of the patient.

Biology and medicine have used animal models to help understand disease for centuries, often by painstakingly breeding lines of animals that have, or are predisposed to have, a specific disease. By taking advantage of recent advances in genetic engineering at UAB and elsewhere, C-PAM's transformative leap will make animal model research directly available to individual patients and their physicians. The use of such models can confirm tentative or novel diagnoses and aid the search for possible treatments, some of which could be unique to the patient.

Underlying the need for C-PAM is the recognition that every undiagnosed disease program at research universities, including UAB's Undiagnosed Diseases Program, faces a huge problem. While they have identified significant numbers of genomic variants, they still lack sufficient functional evidence for clinical reporting and clinical treatment. The C-PAM approach can reveal whether a genomic variant in a patient is causal of the disease, determine its significance for gene function and disease pathophysiology, and identify and evaluate therapeutic targets.

A distinguishing feature of the UAB C-PAM is the establishment of direct interfaces and services for physicians and patients, in addition to services for other scientists. C-PAM will allow a treating physician to request the creation of a customized model for a patient, and the physician can work with C-PAM to further understand the disease and potential treatment.

Operationally, C-PAM will have five interconnected components to bring cutting-edge, precision disease modeling to patients. They are the:

  • Coordinating Component, led by Yoder and Might;
  • Pre/Co-Clinical Component, led by Bruce Korf, M.D., Ph.D., Might and Andy Crouse, Ph.D.;
  • Bioinformatics Component, led by Brittany Lasseigne, Ph.D., and Elizabeth Worthey, Ph.D.;
  • Disease Modeling Unit, led by Yoder, Robert Kesterson, Ph.D., and Craig Powell, M.D., Ph.D.; and
  • Resource and Services Component, led by Deeann Wallis, Ph.D.

The Disease Modeling Unit will host cores that have expertise in each model: 1) frogs, led by Chinbei Chang, Ph.D.; 2) nematode worms, led by Yoder and Courtney Haycraft, Ph.D.; 3) zebrafish, led by John Parant, Ph.D., and Matthew Alexander, Ph.D.; 4) mice, led by Kesterson; and 5) rats, led by Laura Lambert, Ph.D. Powell will oversee efforts in behavioral phenotyping, while Jeremy Foote, Ph.D., will oversee anatomical phenotyping.

C-PAM, Yoder and Might say, will leverage UAB's existing expertise to create a national resource for efficient and cost-effective analysis of pathogenicity of gene variants identified in patients with rare disorders. Its informative models will help pursue disease mechanisms and targeted therapeutics.

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