William C. Nichols, PhD

Associate Director of Research, Division of Human Genetics
Director, National Biological Sample and data Repository for PAH
Professor, UC Department of Pediatrics

bill.nichols@cchmc.org

Visit the Nichols LabVisit the Nichols Lab

About

Biography

My primary research focuses on genetic susceptibility to pulmonary hypertension involving both rare and common genetic variation. My colleagues and I utilize both patient and animal model samples to identify variation in the human genome that leads to susceptibility for this rare, destructive and often fatal condition. In addition, I am studying the genetic susceptibility to Parkinson’s disease as a secondary concentration.

The objectives of my lab team and I involve using genetic methods among diseases to bring about patient-specific customized therapies based on genetic variations that different patients may be harboring. We also hope our genetic approaches to studying disease may lead to innovative treatments based on new pathways we find in our research.

Throughout my career, I’ve had the chance to discover multiple novel disease genes, such as familial amyloidotic polyneuropathy, two different genes for combined factors V and VIII deficiency, thrombotic thrombocytopenic purpura, spheroid body myopathy and numerous novel susceptibility genes for pulmonary arterial hypertension.

I have participated in multiple seminal discoveries for genetic susceptibility to Parkinson’s disease. I developed the world’s largest biorepository of clinical information, biological samples and genetic data for patients with pulmonary arterial hypertension. This biorepository is known as the National Biological Sample and Data Repository for Pulmonary Arterial Hypertension (PAH Biobank).

The National Institutes of Health (NIH) and the National Heart, Lung, and Blood Institute (NHLBI) funded this resource for the PAH research community. The biorepository has led to pioneering research focused on biomarkers, genetics and metabolomics in patients with PAH.

I have more than 30 years of experience in genetics and first joined the Cincinnati Children’s team in 1998. My research has been published in numerous respected journals, such as American Journal of Respiratory and Critical Care Medicine, The Lancet Respiratory Medicine, Circulation, Cell, Nature Genetics, and Nature Communications.

Interests

Dr. Nichols investigates the genetic susceptibility of pulmonary arterial hypertension. His lab was instrumental in identifying the first gene associated with the disorder. He is director of the NHLBI funded National Biological Sample and Data Repository for PAH, an effort to bank biological samples, clinical and genetic data for 3,000 PAH patients. Genetic analysis of murine pulmonary hypertension and Parkinson disease are also ongoing research interests.

Research Areas

Human Genetics

Publications

Allele-specific control of rodent and human lncRNA KMT2E-AS1 promotes hypoxic endothelial pathology in pulmonary hypertension. Tai, YY; Yu, Q; Tang, Y; Sun, W; Kelly, NJ; Okawa, S; Zhao, J; Schwantes-An, TH; Lacoux, C; Torrino, S; et al. Science Translational Medicine. 2024; 16:eadd2029.

Human liver single nuclear RNA sequencing implicates BMPR2, GDF15, arginine, and estrogen in portopulmonary hypertension. Jose, A; Elwing, JM; Kawut, SM; Pauciulo, MW; Sherman, KE; Nichols, WC; Fallon, MB; McCormack, FX. Communications Biology. 2023; 6:826.

Defining the clinical validity of genes reported to cause pulmonary arterial hypertension. Welch, CL; Aldred, MA; Balachandar, S; Dooijes, D; Eichstaedt, CA; Gräf, S; Houweling, AC; Machado, RD; Pandya, D; Prapa, M; et al. Genetics in Medicine. 2023; 25:100925.

Deriving Convergent and Divergent Metabolomic Correlates of Pulmonary Arterial Hypertension. Alotaibi, M; Liu, Y; Magalang, GA; Kwan, AC; Ebinger, JE; Nichols, WC; Pauciulo, MW; Jain, M; Cheng, S. Metabolites. 2023; 13:802.

Low-affinity insulin-like growth factor binding protein 7 and its association with pulmonary arterial hypertension severity and survival. Torres, G; Lancaster, AC; Yang, J; Griffiths, M; Brandal, S; Damico, R; Vaidya, D; Simpson, CE; Martin, LJ; Pauciulo, MW; et al. Pulmonary Circulation. 2023; 13:e12284.

Peripheral Sphingolipids as Potential Biomarkers of Parkinson disease Including Sex-Related Differences (P3-11.007). Ortega, R; Burbulla, L; Mileva, I; Taylor, G; Cuperlovic-Culf, M; Glickman, A; Pullman, M; Scherzer, C; Raymond, D; Miltenyi-Miltenberger, G; et al. Neurology. 2023; 100.

SOX17 Deficiency Mediates Pulmonary Hypertension: At the Crossroads of Sex, Metabolism, and Genetics. Sangam, S; Sun, X; Schwantes-An, TH; Yegambaram, M; Lu, Q; Shi, Y; Cook, T; Fisher, A; Frump, AL; Coleman, A; et al. American Journal of Respiratory and Critical Care Medicine. 2023; 207:1055-1069.

Insulin-like growth factor binding Protein-4: A novel indicator of pulmonary arterial hypertension severity and survival. Torres, G; Yang, J; Griffiths, M; Brandal, S; Damico, R; Vaidya, D; Simpson, CE; Pauciulo, MW; Nichols, WC; Ivy, DD; et al. Pulmonary Circulation. 2023; 13:e12235.

RASA3 is a candidate gene in sickle cell disease-associated pulmonary hypertension and pulmonary arterial hypertension. Prohaska, CC; Zhang, X; Schwantes-An, TH L; Stearman, RS; Hooker, S; Kittles, RA; Aldred, MA; Lutz, KA; Pauciulo, MW; Nichols, WC; et al. Pulmonary Circulation. 2023; 13:e12227.

Genetic counselling and testing in pulmonary arterial hypertension: a consensus statement on behalf of the International Consortium for Genetic Studies in PAH. Eichstaedt, CA; Belge, C; Chung, WK; Gräf, S; Grünig, E; Montani, D; Quarck, R; Tenorio-Castano, JA; Soubrier, F; Trembath, RC; et al. The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology. 2023; 61:2201471.

From the Blog

Heart and Lung

Common Genetic Variant Found for Pulmonary Arterial Hypertension

William C. Nichols, PhD6/30/2019