Education
BA/BS, Saint Louis University, 1995
PhD, University of Nebraska, 2000
MD, University of Nebraska, 2002
Biography
Research
My research focuses in understanding secondary energy deficiency in individuals with the propionate organic acidemias such as Methylmalonic Acidemia and Propionic Acidemia. People with these disorders have a number of long term complication including myopathy, arrhythmias, diabetes, metabolic strokes and cardiomyopathies which we think is related to long term energy deficiencies. They also do poorly when they need to increase their cellular energy levels during illness or other stressful situations with metabolic decompensations.
My basic science laboratory has examined cell lines from patients with propionate organic acidemias and controls and has identified a different responses to low and normal glucose conditions on a RNA level. However, as a population, this change in RNA expression does not pinpoint a particular biochemical pathway beyond a general implication of mitochondrial systems. Clinically individuals appear to have long term complications in high energy organs. As a result, I am now focusing my molecular biology and biochemical studies on examining the intersection of the propionate pathway with the Krebs cycle by looking for sites of interaction and potential moving towards understanding why these patients have such energy deficiency complications. In addition, I am working presently working with our collaborators at HemoShear to design and utilize a liver model system which allows validation and identification of possible therapeutics to treat these disorders with high mortality and morbidity. I also have established relationships with collaborators around the world through my work on guidelines treatment of propionate pathway disorders with whom we can obtain additional tissue if necessary.
Grants
K08: 1K08DK105233-01A1 (PI: Kimberly Chapman)
Source: National Institute of Diabetes and Digestive and Kidney Diseases
We suspect that the Krebs/tricarboxylic acid cycle and propionate pathway, two energy producing pathways that intersect, interact as an association. Here we propose identifying components of this association and then assaying the components as an association. Identifying the components of this association and screening the association for enzyme activity provides a mechanism to screen new treatments for propionate pathway disorders such as propionic acidemia and methylmalonic aciduria, as well as other disorders which affect the Krebs/TCA cycle’s function.
October 2015-October 2018
Publications
Dingle S, Chapman KA, Falk MJ. Fluorescence-activated cell sorting analysis of mitochondrial content, membrane potential, and matrix oxidant burden in human lymphoblastoid cell lines. Methods Mol Biol, 837: 231-239, 2012.
Chapman, KA, Bush WS, Zhang Z. Gene expression in cell lines from Propionic acidemia patients, carrier parents, and controls. Mol Genet Metab 2015 May 8 pii:S1096-7192(15)30011-1 PMID 25963861
Chapman KA, Collado MS, Figler RA, Hoang SA, Armstrong AJ, Cui W, Purdy M, Simmers MB, Yazigi NA, Summar ML, Wamhoff BR, Dash A. Recapitulation of Metabolic defects in a model of Propionic acidemia using patient-derived Primary Hepatocytes. Mol Genet Metab. Accepted
Sutton VR, Chapman KA, Gropman AL, MacLeod E, Stagni K, Summar ML, Ueda K, Ah Mew N, Franks J, Island E, Matern D, Pena L, Smith B, Urv T, Venditti C, Chakrapani A. Chronic Management and Health Supervision in Individuals with Propionic Acidemia. Mol Genet Metab. 2012 Jan;105(1):26-33. Epub 2011 Sep 10.
Pena L, Franks J, Chapman KA, Gropman, AL, Ah Mew N, Chakrapani A, Island E, MacLeod E, Matern D, Smith B, Stagni K, Sutton VR, Ueda K, UrvT, Venditti C, Enns G, Summar ML. Natural History of Propionic Acidemia. Mol Genet Metab. 2012 Jan;105(1):5-9. Epub 2011 Sep 22
Chapman KA, Gropman AL, MacLeod E, Stagni K, Summar ML, Ueda K, Ah Mew N, Franks J, Island E, Matern D, Pena L, Smith B, Sutton VR, UrvT, Venditti C, Chakrapani A. Acute Management in Propionic Acidemia Mol Genet Metab. 2012 Jan;105(1):16-25. Epub 2011 Sep 24.
Baumgartner MR, Hörster F, Assoun M, Ballhausen , Burlina, A, Chapman KA, Dionisi-Vici C, Fowler B, Grünert S, Grünewald S, Haliloglu G, Hochuli M, Honzik T, Huemer M, Karall D, MacDonald A, Martinelli D, Merinero B, Pérez-Cerdá C, Sass J, Scholl-Bürgi S, Skovby F, Valayannopoulos V, Wijburg F, Chakrapani A. Proposed guidelines for the diagnosis and management of methylmalonic and propionic acidemia. Orphanet J Rare Dis. 2014 Sep 2;9(1):130. PMID: 25205257.
Chapman KA. Systemic organic acidemias: Identification, diagnosis, management and long term complications. J Ped. Biochem. 4 (2014)193-200.
Kölker S, Cazorla AG, Valayannopoulos V, Lund AM, Burlina AB, Sykut-Cegielska J, Wijburg FA, Teles EL, Zeman J, Dionisi-Vici C, Bari? I, Karall D, Augoustides-Savvopoulou P, Aksglaede L, Arnoux JB, Avram P, Baumgartner MR, Blasco-Alonso J, Chabrol B, Chakrapani A, Chapman K, I Saladelafont EC, Couce ML, de Meirleir L, Dobbelaere D, Dvorakova V, Furlan F, Gleich F, Gradowska W, Grünewald S, Jalan A, Häberle J, Haege G, Lachmann R, Laemmle A, Langereis E, de Lonlay P, Martinelli D, Matsumoto S, Mühlhausen C, de Baulny HO, Ortez C, Peña-Quintana L, Ramadža DP, Rodrigues E, Scholl-Bürgi S, Sokal E, Staufner C, Summar ML, Thompson N, Vara R, Pinera IV, Walter JH, Williams M, Burgard P. The phenotypic spectrum of organic acidurias and urea cycle disorders. Part 1: the initial presentation. J Inherit Metab Dis. 2015 Apr 15. [Epub ahead of print] PubMed PMID: 25875215.
Kölker S, Valayannopoulos V, Burlina AB, Sykut-Cegielska J, Wijburg FA, Teles EL, Zeman J, Dionisi-Vici C, Bari? I, Karall D, Arnoux JB, Avram P, Baumgartner MR, Blasco-Alonso J, Boy SP, Rasmussen MB, Burgard P, Chabrol B, Chakrapani A, Chapman K, Cortès I Saladelafont E, Couce ML, de Meirleir L, Dobbelaere D, Furlan F, Gleich F, González MJ, Gradowska W, Grünewald S, Honzik T, Hörster F, Ioannou H, Jalan A, Häberle J, Haege G, Langereis E, de Lonlay P, Martinelli D, Matsumoto S, Mühlhausen C, Murphy E, de Baulny HO, Ortez C, Pedrón CC, Pintos-Morell G, Pena-Quintana L, Ramadža DP, Rodrigues E, Scholl-Bürgi S, Sokal E, Summar ML, Thompson N, Vara R, Pinera IV, Walter JH, Williams M, Lund AM, Cazorla AG. The phenotypic spectrum of organic acidurias and urea cycle disorders. Part 2: the evolving clinical phenotype. J Inherit Metab Dis. 2015 Apr 15. [Epub ahead of print] PubMed PMID: 25875216.
Jana Heringer, Vassili Valayannopoulos, Allan M. Lund, Frits A. Wijburg, Peter Freisinger, Lise Aksglaede, Paula Avram, Elena Balmaseda, Ivo Bari?, Eric Bauchart, Matthias R. Baumgartner, Javier Blasco-Alonso, Anaïs Brassier, Peter Burgard, Alberto B. Burlina, Kimberly A. Chapman, Yin-Hsiu Chien, Elisenda Cortès i Saladelafont, Maria L. Couce, Carlo Dionisi-Vici, Dries Dobbelaere, Florian Gleich, Wanda Gradowska, Stephanie Grünewald, Gisela Haege, Johannes Häberle, Wuh-Liang Hwu, Harikleia Ioannou, Daniela Karall, Robin Lachmann, Corinne de Laet, Eveline Langereis, Eduardo López-Laso, Pascale de Lonlay, Shirou Matsumoto, Linda de Meirleir, Chris Mühlhausen, Hélène Ogier de Baulny, Carlos Ortez, Luis Peña-Quintana, Angeles Ruiz, Nicholas Thompson, Roshni Vara, Inmaculada Vives Pinera, Victoria Riches, Adrijan Sarajlija, Manuel Schiff, Marshall L. Summar, Jolanta Sykut-Cegielska, Elisa Leão Teles, John H. Walter, Monique Williams, Jiri Zeman, Brigitte Chabrol, Anupam Chakrapani, Angeles Garcia-Cazorla, and Stefan Kölker. Impact of newborn screening on outcome of organic acidurias. J Inherit Metab Dis. 2015 Dec 21 [Epub ahead of print] PMID 2669403.