Neil A. Hanchard, M.B.B.S., D.Phil.
Center for Precision Health Research
Childhood Complex Disease Genomics Section
M.B.B.S., University Of The West Indies
D.Phil., University Of Oxford
Pediatric Residency, Mayo Clinic, Minnesota
Medical Genetics Residency, Baylor College of Medicine, Houston, Texas
Projects
Childhood-onset Essential Hypertension (COEH)
Childhood-onset essential hypertension – in which there is elevated blood pressure in childhood without an obvious cause - affects 1-2% of all children, accounting for about 40% of all hypertension in children, and is found more often among populations of African- or Hispanic ancestries. Children with COEH are harder to diagnose, but have a strong family history of hypertension. These observations suggest a role for genetics in the development of the disease; however, it is unclear whether this genetic risk mirrors that observed in adults (multiple genes all with small effects) or is more consistent with rare Mendelian diseases that are more striking in childhood (single genes with large effects). Crucially, the treatment of CEOH mirrors that of adults, partly because the underlying pathophysiology is assumed to be the same. We are using next-generation sequencing to explore the model of Mendelian and rare variant contributions to COEH, following up promising candidates with functional characterization and consideration of existing pharmaceutical interventions. We are working alongside national collaborators to expand our COEH cohort and better characterize the vascular and clinical phenotype of gene variant carriers.
Severe Acute Malnutrition (SAM)
Approximately two million children worldwide under the age of five experience severe malnutrition annually, with an estimated 20-30% not surviving. This condition manifests in two classical forms: non-edematous (NESAM or marasmus) and edematous (ESAM, kwashiorkor, or marasmic-kwashiorkor). Despite decades of research, the underlying reasons for the development of ESAM versus NESAM remain elusive, with molecular disparities in their pathophysiology largely unexplored. Our research employs a multi-'omics' approach, focusing on cohorts from diverse ancestries residing in regions where ESAM and SAM are prevalent. Within our laboratory, we are constructing a functional hepatocyte model to simulate fatty liver in ESAM cases, alongside identifying single nucleotide polymorphisms within ESAM and NESAM samples obtained from Jamaica and Malawi. Additionally, we are fostering international collaborations to establish a comprehensive repository of SAM samples, collaborating with researchers in SAM high-incidence countries to create a Kwashiorkor Study Network. Through this we hope to better understand the etiologic and pathophysiologic differences between ESAM and NESAM. The findings of this study will be used to assist in the development of targeted interventions designed to correct the unique metabolic disturbances of kwashiorkor.
Sickle Cell Disease Alloimmunization
Sickle cell disease (SCD) is one of the most common genetic diseases in the world, with high mortality rates and a lowered life expectancy. Regular transfusion of red blood cells (RBCs) is a mainstay of treatment; however, repeated transfusions increase the risk of developing alloantibodies against donor RBCs. RBC alloimmunization is seen in ~6-9% of multiply-transfused SCD individuals, with some studies reporting rates twice as high. In the most severe cases, transfused patients develop alloantibodies with almost every new transfusion – so called transfusion ‘super-responders’; this creates a major challenge to find compatible blood for future transfusions. Fundamentally, the reason some individuals develop alloantibodies when most do not, remains unclear. In our previous studies, we identified a genome-wide significant association between an intergenic locus on chromosome 5q33 and being a transfusion responder and replicated this in a second cohort. To our knowledge, this remains the only replicated genetic locus influencing risk of being an alloimmunization responder in SCD. We are utilizing a multiomics approach to validate the functional consequence(s) of our risk locus. We are also applying trans- and local-ancestry admixture mapping models to the NHLBI-sponsored Trans-Omics for Precision Medicine (TOPMed) program - a cohort of 2,800 SCD individuals from six geographically diverse sites across Brazil that includes ~800 transfusion responders characterized in the same way as our original SCD alloimmunization cohort. We are performing local ancestry association to identify novel risk alleles, replicate our initial GWAS hit, understand the effect of ancestral background on alloimmunization risk, and develop a genetic (polygenic) risk score for alloimmunization. Collectively, these efforts seek to provide insight to the immunological mechanisms underlying the increased alloimmunization risk, and in so doing, advance much needed therapeutic targets to improve the safety of an important clinical intervention.
Childhood Complex Disease Genomics Section Staff
- Technical Lab Manager
- Childhood Complex Disease Genomics Section
- Geneticist (Counselor)
- Childhood Complex Disease Genomics Section
- Staff Scientist
- Childhood Complex Disease Genomics Section
- Staff Scientist
- Childhood Complex Disease Genomics Section
CAfGEN Graduate Students
- CAfGEN Fellow
- University of Botswana
- CAfGEN Fellow
- University of Botswana
- CafGEN Fellow
- University of Botswana
- CAfGEN Fellow
- Makerere College of Health Sciences
Fellows
- Predoctoral IRTA Fellow, CAfGEN Fellow
- Childhood Complex Disease Genomics Section
- Postbaccalaureate Fellow
- Childhood Complex Disease Genomics Section
- Predoctoral IRTA Fellow
- Childhood Complex Disease Genomics Section
- Postbaccalaureate Fellow
- Childhood Complex Disease Genomics Section
- Postbaccalaureate Fellow
- Childhood Complex Disease Genomics Section
- Postbaccalaureate Fellow
- Childhood Complex Disease Genomics Section
- Postbaccalaureate Fellow
- Childhood Complex Disease Genomics Section
- Postdoctoral Fellow
- Childhood Complex Disease Genomics Section
- Postdoctoral Fellow
- Childhood Complex Disease Genomics Section
Last updated: September 18, 2024