Dr. Haas’s early work in the 1980’s was in the area of Rett syndrome. He continues this work today, studying a cohort of 100 girls and women with Rett Syndrome and the implications that mitochondrial dysfunction may have in contributing to it. Then, in 1994, Dr. Haas established the Leigh’s Center at UC San Diego.
Leigh syndrome is a devastating disorder caused by defects in mitochondrial metabolism. As a result of evaluating children for Leigh syndrome, a number of non-Leigh Syndrome mitochondrial disorders were identified, thus establishing the further need to provide care for and study of patients with mitochondrial disease. In 1996, Dr. Haas collaborated with Dr. Richard Naviaux to help establish the UCSD Mitochondrial and Metabolic Disease Center (MMDC).
Currently the MMDC is an international leader in the diagnosis, treatment and research (including clinical trials) of metabolic disorders.
In 1999 Dr. Haas worked Dr. Naviaux again to identify mitochondrial DNA polymerase mutations as the cause of the first reported mitochondrial disease, Alper’s syndrome. Mitochondrial DNA depletion syndromes, polymerase defects and abnormalities of the mitochondrial replisome are now known to be common causes of mitochondrial disease in children and adults. He remains actively involved in research in this area to this day.
Recent research out of the MMDC has identified a subset of children with Autism who also have mitochondrial dysfunction. In a recent project, Dr. Haas was UCSD principal investigator in a study looking mitochondrial dysfunction in children with autism.
Current research in collaboration with researchers at the Sanford-Burnham Institute is focused on creating stem cells from mitochondrial disease cell lines. The aim is to create neurons and muscle cells carrying mitochondrial disease mutations as model systems for drug development.
It is difficult to discuss Dr. Haas’s research interests without linking them to his clinical activities since they are so closely intertwined. One such example is the “Intravenous Levetiracetam for the Treatment of Neonatal Seizures” study funded by the Thrasher Foundation. Dr. Haas recently completed a phase I/II pharmacokinetic study of a new anticonvulsant drug, levetiracetam in the treatment of neonatal seizures. Results of data from this study should improve the care of neonates with seizures. The development of EEG remote video monitoring was an important part of this project. benefiting babies in the major neonatal units throughout San Diego.
Teaching the next generation of physicians is particularly important. Dr. Haas is the director of the North American Mitochondrial Disease Consortium fellowship program funded by the NIH and established to train physicians to work in the field of mitochondrial medicine.
Selected Peer-Reviewed Publications
1) Haas RH, Thompson J, Morris BS, Conright K and Andrews T. Pyruvate dehydrogenase activity in osmotically shocked rat brain mitochondria: stimulation by oxaloacetate. J Neurochemistry 50(3):673-680, 1988. PMID: 3339345
2) Haas RH, Nasirian F, Nakano K, Ward D et al. Low platelet mitochondrial complex I and complex II/III activity in early untreated Parkinson’s disease. Annals of Neurology 37:714-722, 1995. PMID: 7778844
3) Naviaux RK, Nyhan WL, Barshop BA, Poulton J, Markusic D, Karpinski NC and Haas RH. Mitochondrial DNA polymerase deficiency and mitochondrial DNA depletion in a child with Alpers syndrome. Annals of Neurology 45:1, 54-58, 1999. PMID: 9894877
4) Spruijt L, Naviaux RK, McGowan KA, Nyhan WL, Sheean G, Haas RH, Barshop BA. Nerve conduction changes in patients with mitochondrial diseases treated with Dichloroacetate. Muscle Nerve 24:916-924, 2001. PMID: 11410919
5) Shults CW, Oakes D, Kieburtz K, Beal FM, Haas R, Plumb S, Juncos JL, Nutt J, Shoulson I, Carter J, Kompoliti K, Perlmutter JS, Reich S, Stern M, Watts RL, Kurlan R, Molho E, Harrison M, Lew M, and the Parkinson Study Group. Effects of Coenzyme Q10 in early Parkinson disease. Evidence of slowing of the functional decline. Arch Neurol 59:1541-1550, 2002. PMID: 12374491
6) Barshop BA, Naviaux RK, McGowan KA, Levine F, Nyhan WL, Loupis-Geller A, Haas RH. Chronic treatment of mitochondrial disease patients with Dichloroacetate. Molecular Genetics and Metabolism 83:138-149, 2004. PMID: 15464428
7) Lim KS, Naviaux RK, Haas RH. Quantitative mitochondrial DNA mutation analysis by denaturing HPLC. Clin Chem 53(6):1046-52, 2007. PMID: 17446331
8) Haas RH, Parikh S, Falk MJ, Saneto RP, Wolf NI, Darin N and Cohen BH. Mitochondrial Disease: A practical approach for primary care physicians. Pediatrics 120(6):1326-1333, 2007. PMID: 18055683
9) Haas RH, Parikh S, Falk MJ, Saneto RP, Wolf NI, Darin N, Wong LJ, Cohen B and Naviaux R. The in-depth evaluation of suspected mitochondrial disease. Molecular Genetics and Metabolism 94(1):16-37, 2008. PMID: 18243024
10) Lim KS, Naviaux RK, Wong S and Haas R. Pitfalls in the denaturing high-performance liquid chromatography analysis of mitochondrial DNA mutation. Journal of Molecular Diagnostics, 10: 1, 102-108, 2008. PMID: 18165269
11) Parikh S, Saneto R, Falk MJ, Anselm I, Cohen BH, Haas R, Medicine Society TM. A modern approach to the treatment of mitochondrial disease. Curr Treat Options Neurol. Nov;11(6):414-30, 2009.
12) Haas RH. Autism and mitochondrial disease. Dev Disabil Res Rev. 2010 Jun;16(2):144-53. PMID: 20818729
13) Powers WJ, Haas RH, Le T, Videen TO, Markham J, Perlmutter JS.Platelet mitochondrial complex I and I+III activities do not correlate with cerebral mitochondrial oxidative metabolism. J Cereb Blood Flow Metab. Jan;31(1):e1-5, 2011 PMID:20959851
14) Du A, Naviaux RK, Le T, Xu C, Sommer SS, Haas RH. Fibroblast immuno-diagnosis of cytochrome oxidase (COX) deficiency in mitochondrial disease. Mitochondrion. 2011 May;11(3):430-6, 2011. PMID: 21187165
15) Chen X, Thorburn DR, Wong LJ, Vladutiu GD, Haas RH, Le T, Hoppel C, Sedensky M, Morgan P, Hahn SH.Quality improvement of mitochondrial respiratory chain complex enzyme assays using Caenorhabditis elegans. Genet Med. Sep;13(9):794-9. 2011. PMID: 21633293
16) Sharpe CM, Capparelli EV, Mower A, Farrell MJ, Soldin SJ, Haas RH. A seven-day study of the pharmacokinetics of intravenous levetiracetam in neonates: marked changes in pharmacokinetics occur during the first week of life. Pediatr Res. 2012 Jul;72(1):43-9. doi: 10.1038/pr.2012.51. Epub 2012 Apr 11.
17) Shangle CE, Haas RH, Vaida F, Rich WD, Finer NN. Effects of endotracheal intubation and surfactant on a 3-channel neonatal electroencephalogram. J Pediatr. 2012 Aug;161(2):252-7. doi:0.1016/j.jpeds.2012.02.014. Epub 2012 Mar 16.
18)Smith M, Flodman PL, Gargus JJ, Simon MT, Verrell K, Haas R, Reiner GE, Naviaux R, Osann K, Spence MA, Wallace DC. Mitochondrial and ion channel gene alterations in autism. Biochim Biophys Acta 2012 Apr (7) doi:10.1016.
19) Zhang C, Huang VH, Simon M, Sharma LK, Fan W, Haas R, Wallace DC, Bai Y and Huang T. Heteroplasmmic mutations of the mitochondrial genome cause paradoxical effects on mitochondrial functions. FASEB J 26, 4914-4924, 2012.
20) Parikh S, Goldstein A, Koenig MK, Scaglia F, Enns GM, Saneto R; for the Mitochondrial Medicine Society Clinical Directors Working Group; Clinical Director's Work Group. Practice patterns of mitochondrial disease physicians in North America. Part 1: Diagnostic and clinical challenges. Mitochondrion. 2013 Jul 26. doi:pii: S1567-7249(13)00215-8. 10.1016/j.mito.2013.07.116. [Epub aheadof print] PubMed PMID: 23891656.
21) Zhang Z, Tsukikawa M, Peng M, Polyak E, Nakamaru-Ogiso E, Ostrovsky J, McCormack S, Place E, Clarke C, Reiner G, McCormick E, Rappaport E, Haas R, Baur JA, Falk MJ. Primary respiratory chain disease causes tissue-specific dysregulation of the global transcriptome and nutrient-sensing signaling network. PLoS One. 2013 Jul 24;8(7):e69282. doi: 10.1371/journal.pone.0069282. Print 2013. PubMed PMID: 23894440; PubMed Central PMCID: PMC3722174.
22) Kostrominova TY, Reiner DS, Haas RH, Ingermanson R, McDonough PM. Automated methods for the analysis of skeletal muscle fiber size and metabolic type. Int Rev Cell Mol Biol. 2013;306:275-332. doi: 10.1016/B978-0-12-407694-5.00007-9. PubMed PMID: 24016528.
23) Milone M, Klassen BT, Landsverk ML, Haas RH, Wong LJ. Orthostatic Tremor, Progressive External Ophthalmoplegia, and Twinkle. JAMA Neurol. 2013 Sep 23. doi: 10.1001/jamaneurol.2013.3521. [Epub ahead of print] PubMed PMID: 24061067.
24) Parikh S, Goldstein A, Koenig MK, Scaglia F, M Enns G, Saneto R, Anselm I, Collins A, Cohen BH, DeBrosse SD, Dimmock D, Falk MJ, Ganesh J, Greene C, Gropman AL, Haas R, Kahler SG, Kamholz J, Kendall F, Korson MS, Mattman A, Milone M, Niyazov D, Pearl PL, Reimschisel T, Salvarinova-Zivkovic R, Sims K, Tarnopolsky M, Tsao CY, Hove JV, Walsh L and Wolfe LA. Practice patterns of mitochondrial disease physicians in North America: Part 1: Diagnostic and clinical challenges. Mitochondrion (2014).