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Investigator

Center for Precision Health Research

Clinical Investigator

Center for Precision Health Research

Head

Childhood Complex Disease Genomics Section

Education

M.B.B.S., University Of The West Indies, 1999

D.Phil., University Of Oxford, 2004

Biography

Dr. Hanchard received his MD (MBBS with Honours) from the University of the West Indies in Kingston, Jamaica, after which he was award the Jamaica Rhodes Scholarship to the University of Oxford, UK. There, he completed a D.Phil. in Human Genetics and Clinical Medicine in the laboratory of Prof. Dominic Kwiatkowski, where he worked on population differentiation, genome variation, and natural selection in the Major Histocompatibility Complex. After returning to Jamaica to study sickle cell disease and severe childhood malnutrition as a clinical research scholar, he moved to the US to do his pediatric residency at the Mayo Clinic in Rochester, Minnesota, before completing a Medical Genetics fellowship at Baylor College of Medicine (BCM) in Houston, Texas. Soon after, he started his own lab as a tenure-track physician scientist in the Department of Molecular and Human genetics at BCM, focusing on the genetics of complex childhood diseases in diverse populations. In addition, Dr Hanchard cared for patients with rare genetic disorders and directed a medium throughput core genetics laboratory, in addition to mentoring and teaching graduate students, medical residents, and medical students. His research has provided insight to the population genetics of the mutation that causes sickle cell disease, identified novel genes in the development of congenital cardiovascular disorders and rare Mendelian disorders, and made inroads to understanding the pathogenesis of diabetic embryopathy, severe childhood malnutrition and transfusion alloimmunization in sickle cell disease.

Dr. Hanchard has served in multiple advisory positions for research institutions, the American Society for Human Genetics (ASHG), and genetics journals, and he was the first Early-Career board member of ASHG. He is a fellow of the American College of Medical Genetics and the Society for Pediatric Research. Dr. Hanchard is the current Chair of the Genome Analysis working group of the H3Africa Consortium and an NIH Distinguished Scholar. 

Childhood Complex Disease Genomics Section

CCDGS - Our Approach diagram

 

The CCDGS is a translational genomics research lab using human genetics and genomics to better understand the pathophysiology of childhood diseases, particularly in diverse populations. Traditionally, genomic studies in children have focused on rare Mendelian phenotypes; however, the unique developmental context and reduced environmental exposure of children over time, provides fertile ground for genetic discovery and therapeutic investigation. At the same time, there is a general lack of diversity among genomic studies, with populations of African ancestry being particularly underrepresented, despite harboring an abundance of genomic diversity and unique clinical presentations. Our approach is to start with epidemiological evidence for differences between individuals and formulate plausible genetic models of disease. We then work with global and national collaborators to recruit well-phenotyped cohorts, to which we apply genomic, epigenomic, and transcriptomic technologies alongside population and quantitative genetics to identify the genes and gene-pathways that drive disease. Newly discovered genes are then validated, and the underlying mechanisms probed. This approach facilitates our ultimate goal of translating mechanistic understanding into therapeutic strategies – providing personalized medicine by going from bedside to bench and back.

Projects

Severe Acute Malnutrition (SAM)

Approximately two million children worldwide under the age of five become severely malnourished every year – an estimated 20-30% of whom do not survive. Classically, severe acute malnutrition is described as being either non-edematous (NESAM or marasmus) or the systemically deleterious edematous (ESAM, kwashiorkor, or marasmic-kwashiorkor) form. Despite decades of study, the reason some children develop ESAM and others NESAM remains unanswered, and molecular differences in the pathophysiology of the two types remain largely unexplored. We are applying our multi-’omics’ approach to cohorts from populations of diverse ancestries where ESAM and SAM remain prevalent. Through this we hope to better understand and inform the etiologic and pathophysiologic differences between ESAM and NESAM.

Severe Acute Childhood Malnutrition diagram

 

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.

COEH diagram

 

Sickle Cell Disease (SCD)

Sickle Cell Disease (SCD) is a recessive disorder of hemoglobin and one of the most common single gene disorders in the world. Despite being caused by a single pathogenic variant in the beta-globin gene and being the first described ‘molecular disease’, there is incredible variability in the consequences and manifestations of the disease that remain understudied. We are using genomics to explore the genetic factors contributing to variability in the response to red blood cell transfusions and the expression of beta-globin genes.

 

Sickle Cell Disease diagram

 

Collaborative African Genomics Network (CAfGEN)

We are a part of a multi-national project funded by the NIH, Wellcome Trust, and African Academy of Sciences (AAS) known as the Human Health and Heredity in Africa (H3Africa) Consortium. The goals of the consortium are to establish and grow genomics and genetics technologies and expertise in Africa for the purposes of advancing human health and disease (www.h3africa.org; @H3Africa). Our project – the Collaborative African Genomics Network (CAfGEN; @CAfGEN1) is based in Botswana and includes clinical and/or research sites in Botswana, Uganda, eSwatini, and the United States. The main focus of the consortium is pediatric HIV/AIDS, which affects more than 1 million children in Africa under the age of 15 and imposes a significant health burden on affected countries. Collectively, the project seeks to use genetics and genomics to better understand the molecular drivers of the progression from HIV infection to AIDS and to improve the diagnosis of active tuberculosis disease in African children. These research aims also provide opportunities for training and development of genomics knowledge in the host countries. CAfGEN is using transcriptomics and genomics to describe the genetic ancestry and variation within African genomes and using the resulting information to refine the genes, pathways, and environmental influences involved in disease progression.

 

Collaborative African Genomics Network (CAfGEN)

 

Publications

Mwesigwa S, Williams L, Retshabile G, Katagirya E, Mboowa G, Mlotshwa B, Kyobe S, Kateete DP, Wampande EM, Wayengera M, Mpoloka SW, Mirembe AN, Kasvosve I, Morapedi K, Kisitu GP, Kekitiinwa AR, Anabwani G, Joloba ML, Matovu E, Mulindwa J, Noyes H, Botha G; Collaborative African Genomics Network (CAfGEN); TrypanoGEN Research Group, Brown CW, Mardon G, Matshaba M, Hanchard NA. Unmapped exome reads implicate a role for Anelloviridae in childhood HIV-1 long-term non-progression. npj Genom Med. 2021 Mar 19;6(1):24. doi: 10.1038/s41525-021-00185-w.

Murdock DR, Dai H, Burrage LC, Rosenfeld JA, Ketkar S, Müller MF, Yépez VA, Gagneur J, Liu P, Chen S, Jain M, Zapata G, Bacino CA, Chao HT, Moretti P, Craigen WJ, Hanchard NA; Undiagnosed Diseases Network, Lee B. Transcriptome-directed analysis for Mendelian disease diagnosis overcomes limitations of conventional genomic testing. J Clin Invest. 2021 Jan 4;131(1):e141500. doi: 10.1172/JCI141500.

A Choudhury, S Aron, L Botigué, D Sengupta, G Botha, T Bensellak, G Wells, J Kumuthini, D Shriner, YJ Fakim, AW Ghoorah, E Dareng, T Odia, O Falola, E Adebiyi, S Hazelhurst, G Mazandu, OA Nyangiri, M Mbiyavanga, A Benkahla, SK Kassim, N Mulder, SN Adebamowo, ER Chimusa, RA Gibbs, D Muzny46, G Metcalf, TrypanoGEN Research Group‡, C Rotimi, M Ramsay, H3Africa Consortium‡, A Adeyemo, Z Lombard^, NA Hanchard^, High Depth African Genomes Inform Human Migration and Health. Nature. 2020 Oct;586(7831):741-748. doi: 10.1038/s41586-020-2859-7. Epub 2020 Oct 28. 

KV Schulze, S Swaminathan, S Howell, A Jajoo, O Brown, R Sadat, N Hall, L Zhao, K Marshall, ME Reid, X Wang, JW Belmont, Y Guan, CA McKenzie, M Manary, I Trehan, NA Hanchard^. Edematous severe acute malnutrition is characterized by hypomethylation of DNA. Nat Comms. 2019 Dec 19;10(1):5791. doi: 10.1038/s41467-019-13433-6.

KV Schulze, A Bhatt, MS Azamian, N Sundgren, G Zapata, P Hernandez, K Fox, JR Kaiser, JW Belmont, NA Hanchard^. Aberrant DNA methylation as a diagnostic biomarker of diabetic embryopathy. Genet in Med. 2019 Nov;21(11):2453-2461; PMID: 30992551 

G Retshabile, B Mlotshwa, S Swaminathan, L Williams, S Mwesigwa, G Mboowa, A Kekitiinwa, M Joloba, F Yu, G Anabwani, SW Mpoloka, G Mardon, NA Hanchard^ for the Collaborative African Genomics Network of the H3Africa Consortium. Whole exome sequencing reveals uncaptured variation and distinct ancestry in the Southern African population of Botswana. Am J Hum Gen, 2018, May 3;102(5):731-743. PMID: 29706352; PMCID: PMC5986695

Sickle Cell Disease Ontology Working Group (NA Hanchard as co-author). The Sickle Cell Disease Ontology: Enabling universal sickle cell-based knowledge representation. Database (Oxford). 2019 Jan 1;2019:baz118; PMID: 31769834

L Williams, A Chen, J Moulds, Z Qi, S Hooker, S Campbell-Lee, R Kittles, Y Guan, NA Hanchard. A Genome-Wide Screen of RBC Alloimmunization Status in Sickle Cell Disease Reveals African-Ancestry-Limited Association at a locus on Chromosome 5. Blood Adv. 2018 Dec 26;2(24):3637-364; PMCID: PMC6306880

Mnika K, Mazandu GK, Jonas M, Pule GD, Chimusa ER, Hanchard NA, Wonkam A. Hydroxyurea-Induced miRNA Expression in Sickle Cell Disease Patients in Africa. Front Genet. 2019;10:509. doi: 10.3389/fgene.2019.00509. eCollection 2019. PubMed PMID: 31231425; PubMed Central PMCID: PMC6568309.

AH Li*, NA Hanchard*, M Azamian, S Fernbach, G Zapata, P Hernandez, DR Parekh, WJ Franklin, DJ Penny, CD Fraser, JR Lupski, RA Gibbs, E Boerwinkle, JW Belmont. Whole Exome Sequencing in 342 Left-Sided Lesion Cases Reveals Extensive Genetic Heterogeneity and Complex Inheritance Patterns Genome Med 2017 Oct 31;9(1):95. PMID: 29089047 PMCID: PMC5664429

Li AH, Hanchard NA, Azamian M, D'Alessandro LCA, Coban-Akdemir Z, Lopez KN, Hall NJ, Dickerson H, Nicosia A, Fernbach S, Boone PM, Gambin T, Karaca E, Gu S, Yuan B, Jhangiani SN, Doddapaneni H, Hu J, Dinh H, Jayaseelan J, Muzny D, Lalani S, Towbin J, Penny D, Fraser C, Martin J, Lupski JR, Gibbs RA, Boerwinkle E, Ware SM, Belmont JW. Genetic architecture of laterality defects revealed by whole exome sequencing. Eur J Hum Genet. 2019 Apr;27(4):563-573. doi: 10.1038/s41431-018-0307-z. Epub 2019 Jan 8. PubMed PMID: 30622330; PubMed Central PMCID: PMC6460585.

Hanchard NA, Swaminathan S, Bucasas K, Furthner D, Fernbach S, Azamian MS, Wang X, Lewin M, Towbin JA, D'Alessandro LC, Morris SA, Dreyer W, Denfield S, Ayres NA, Franklin WJ, Justino H, Lantin-Hermoso MR, Ocampo EC, Santos AB, Parekh D, Moodie D, Jeewa A, Lawrence E, Allen HD, Penny DJ, Fraser CD, Lupski JR, Popoola M, Wadhwa L, Brook JD, Bu'Lock FA, Bhattacharya S, Lalani SR, Zender GA, Fitzgerald-Butt SM, Bowman J, Corsmeier D, White P, Lecerf K, Zapata G, Hernandez P, Goodship JA, Garg V, Keavney BD, Leal SM, Cordell HJ, Belmont JW, McBride KL. A genome-wide association study of congenital cardiovascular left-sided lesions shows association with a locus on chromosome 20. Hum Mol Genet. 2016 Jun 1;25(11):2331-2341. doi: 10.1093/hmg/ddw071. Epub 2016 Mar 9. PubMed PMID: 26965164; PubMed Central PMCID: PMC5081047.


 

Childhood Complex Disease Genomics Section Staff

Apart Haldipur
Aparna Haldipur, M.S.
  • Research Technician / Lab Manager
  • Childhood Complex Disease Genomics Section
Mashid Zamian
Mashid Azamian, M.D.
  • Medical Research Officer
  • Childhood Complex Disease Genomics Section
Edmund Wonkam
Edmond Wonkam, M.D., Ph.D.
  • Postdoctoral Fellow
  • Childhood Complex Disease Genomics Section
Yixing Han
Yixing Han, Ph.D.
  • Staff Scientist
  • Childhood Complex Disease Genomics Section

Graduate Students

Natasha Lie
Natasha Lie
  • Predoctoral IRTA
  • Baylor College of Medicine
Thabo Diphoko
Thabo Diphoko
  • CAfGEN Fellow
  • Baylor College of Medicine
Savannah Mwesigwa
Savannah Mwesigwa
  • CafGEN Fellow
  • Baylor College of Medicine
Gaseene Sebetso
Gaseene Sebetso
  • CAfGEN Fellow
  • Baylor College of Medicine
Pamela Lurie
Pamela Lurie
  • Predoctoral IRTA
  • Baylor College of Medicine
Marion Amajul
Marion Amajul
  • CafGEN Fellow
  • Baylor College of Medicine
Lesedi Williams
Lesedi Williams
  • CafGEN Fellow
  • Baylor College of Medicine
John Mukisa
John Mukisa, M.D.
  • CAfGEN Fellow
  • Baylor College of Medicine

Post-Baccalaureate Students

Toluwani Taiwo
Toluwani Taiwo
  • Non-BCM Student Observer
  • Baylor College of Medicine

Last updated: June 15, 2021