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Curt Scharfe

Associate Professor of Genetics

Contact Information

Curt Scharfe, MD, PhD, FACMG

Mailing Address

  • Genetics

    PO Box 208005, 333 Cedar Street

    New Haven, CT 06520-8005

    United States

Research Summary

Our laboratory develops new tools and genomic approaches for molecular screening and diagnostics and the study of disease pathogenesis. We couple experimental and computational techniques to fully integrate all steps of highly multiplexed molecular assays, which include nucleic acid extraction from small and challenging clinical samples (e.g., dried blood spots, plasma), targeted (multi-gene panels, exome, microarrays) and genome sequencing, detection of rare single nucleotide and copy number variants, and data interpretation in the context of clinical findings. We use laboratory automation to increase assay precision and speed, and work on implementing these techniques into rapid disease screening and diagnostics. Our lab is located in a highly translational setting next to the Yale DNA Diagnostic Laboratory. We work closely with the Yale Center for Genome Analysis (YCGA) and collaborate with clinical colleagues and researcher at Yale and other institutions. Please read here about our most recent projects.

We are interested in collaborations of all sorts including clinical medicine, genetics and genomics, biochemistry, technology development, chemical and electrical engineering, statistics and computational sciences. We seek highly motivated students and postdoctoral candidates to join a multi-disciplinary team of experimental and computational scientists in a highly translational setting at the Yale Genetics Department. Please feel free to contact for open positions.

Extensive Research Description

Complete List of Published Work in MyBibliography:

  1. Peng G, Shen P, Gandotra N, Le A, Fung E, Jelliffe-Pawlowski L, Davis RW, Enns GM, Zhao H, Cowan TM, Scharfe C. Combining newborn metabolic and DNA analysis for second-tier testing of methylmalonic acidemia. Genet Med. 2019 Apr;21(4):896-903. doi: 10.1038/s41436-018-0272-5. Epub 2018 Sep 13. PubMed PMID: 30209273; PubMed Central PMCID: PMC6416784.
  2. Peng G, de Fontnouvelle CA, Enns GM, Cowan TM, Zhao H, Scharfe C. Elevated methylmalonic acidemia (MMA) screening markers in Hispanic and preterm newborns. Mol Genet Metab. 2019 Jan;126(1):39-42. doi: 10.1016/j.ymgme.2018.11.006. Epub 2018 Nov 10. PubMed PMID: 30448007; PubMed Central PMCID: PMC6361520.
  3. Tan SK, Shen P, Lefterova MI, Sahoo MK, Fung E, Odegaard JI, Davis RW, Pinsky BA, Scharfe C. Transplant Virus Detection Using Multiplex Targeted Sequencing. J Appl Lab Med. 2018 Mar;2(5):757-769. doi: 10.1373/jalm.2017.024521. PubMed PMID: 31245786; PubMed Central PMCID: PMC6594177.
  4. Karaa A, Rahman S, Lombès A, Yu-Wai-Man P, Sheikh MK, Alai-Hansen S, Cohen BH, Dimmock D, Emrick L, Falk MJ, McCormack S, Mirsky D, Moore T, Parikh S, Shoffner J, Taivassalo T, Tarnopolsky M, Tein I, Odenkirchen JC, Goldstein A.Common data elements for clinical research in mitochondrial disease: a National Institute for Neurological Disorders and Stroke project. J Inherit Metab Dis. 2017 May;40(3):403-414. doi: 10.1007/s10545-017-0035-5. Epub 2017 Mar 16. PubMed PMID: 28303425.
  5. Rychkova A, Buu MC, Scharfe C, Lefterova MI, Odegaard JI, Schrijver I, Milla C, Bustamante CD. Developing Gene-specific Meta-predictor of Variant Pathogenicity. bioRxiv. 2017 March; doi:
  6. Sylvester KG, Kastenberg ZJ, Moss RL, Enns GM, Cowan TM, Shaw GM, Stevenson DK, Sinclair TJ, Scharfe C, Ryckman KK, Jelliffe-Pawlowski LL. Acylcarnitine Profiles Reflect Metabolic Vulnerability for Necrotizing Enterocolitis in Newborns Born Premature. J Pediatr. 2017 Feb;181:80-85.e1. doi: 10.1016/j.jpeds.2016.10.019. Epub 2016 Nov 8. PubMed PMID: 27836286; PubMed Central PMCID: PMC5538349.
  7. Lefterova MI, Shen P, Odegaard JI, Fung E, Chiang T, Peng G, Davis RW, Wang W, Kharrazi M, Schrijver I, Scharfe C. Next-Generation Molecular Testing of Newborn Dried Blood Spots for Cystic Fibrosis. J Mol Diagn. 2016 Mar;18(2):267-82. doi: 10.1016/j.jmoldx.2015.11.005. Epub 2016 Feb 1. PubMed PMID: 26847993; PubMed Central PMCID: PMC4816703.
  8. Wilson KD, Shen P, Fung E, Karakikes I, Zhang A, InanlooRahatloo K, Odegaard J, Sallam K, Davis RW, Lui GK, Ashley EA, Scharfe C, Wu JC. A Rapid, High-Quality, Cost-Effective, Comprehensive and Expandable Targeted Next-Generation Sequencing Assay for Inherited Heart Diseases. Circ Res. 2015 Sep 11;117(7):603-11. doi: 10.1161/CIRCRESAHA.115.306723. Epub 2015 Aug 11. PubMed PMID: 26265630; PubMed Central PMCID: PMC4568077.
  9. Falk MJ, Shen L, Gonzalez M, Leipzig J, Lott MT, Stassen AP, Diroma MA, Navarro-Gomez D, Yeske P, Bai R, Boles RG, Brilhante V, Ralph D, DaRe JT, Shelton R, Terry SF, Zhang Z, Copeland WC, van Oven M, Prokisch H, Wallace DC, Attimonelli M, Krotoski D, Zuchner S, Gai X. Mitochondrial Disease Sequence Data Resource (MSeqDR): a global grass-roots consortium to facilitate deposition, curation, annotation, and integrated analysis of genomic data for the mitochondrial disease clinical and research communities. Mol Genet Metab. 2015 Mar;114(3):388-96. doi: 10.1016/j.ymgme.2014.11.016. Epub 2014 Dec 4. Review. PubMed PMID: 25542617; PubMed Central PMCID: PMC4512182.
  10. Schlecht U, Suresh S, Xu W, Aparicio AM, Chu A, Proctor MJ, Davis RW, Scharfe C, St Onge RP. A functional screen for copper homeostasis genes identifies a pharmacologically tractable cellular system. BMC Genomics. 2014 Apr 5;15:263. doi: 10.1186/1471-2164-15-263. PubMed PMID: 24708151; PubMed Central PMCID: PMC4023593.
  11. Shen P, Wang W, Chi AK, Fan Y, Davis RW, Scharfe C. Multiplex target capture with double-stranded DNA probes. Genome Med. 2013;5(5):50. doi: 10.1186/gm454. eCollection 2013. PubMed PMID: 23718862; PubMed Central PMCID: PMC3706973.
  12. Peng G, Fan Y, Palculict TB, Shen P, Ruteshouser EC, Chi AK, Davis RW, Huff V, Scharfe C, Wang W. Rare variant detection using family-based sequencing analysis. Proc Natl Acad Sci U S A. 2013 Mar 5;110(10):3985-90. doi: 10.1073/pnas.1222158110. Epub 2013 Feb 20. PubMed PMID: 23426633; PubMed Central PMCID: PMC3593912.
  13. St Onge R, Schlecht U, Scharfe C, Evangelista M. Forward chemical genetics in yeast for discovery of chemical probes targeting metabolism. Molecules. 2012 Nov 5;17(11):13098-115. doi: 10.3390/molecules171113098. Review. PubMed PMID: 23128089; PubMed Central PMCID: PMC3539408.
  14. Zhang N, Xu Y, O'Hely M, Speed TP, Scharfe C, Wang W. SRMA: an R package for resequencing array data analysis.Bioinformatics. 2012 Jul 15;28(14):1928-30. doi: 10.1093/bioinformatics/bts286. Epub 2012 May 10. PubMed PMID: 22581181; PubMed Central PMCID: PMC3389772.
  15. Shen P, Wang W, Krishnakumar S, Palm C, Chi AK, Enns GM, Davis RW, Speed TP, Mindrinos MN, Scharfe C. High-quality DNA sequence capture of 524 disease candidate genes. Proc Natl Acad Sci U S A. 2011 Apr 19;108(16):6549-54. doi: 10.1073/pnas.1018981108. Epub 2011 Apr 5. PubMed PMID: 21467225; PubMed Central PMCID: PMC3080966.
  16. Wang W, Shen P, Thiyagarajan S, Lin S, Palm C, Horvath R, Klopstock T, Cutler D, Pique L, Schrijver I, Davis RW, Mindrinos M, Speed TP, Scharfe C. Identification of rare DNA variants in mitochondrial disorders with improved array-based sequencing. Nucleic Acids Res. 2011 Jan;39(1):44-58. doi: 10.1093/nar/gkq750. Epub 2010 Sep 15. PubMed PMID: 20843780; PubMed Central PMCID: PMC3017602.
  17. Farias-Hesson E, Erikson J, Atkins A, Shen P, Davis RW, Scharfe C, Pourmand N. Semi-automated library preparation for high-throughput DNA sequencing platforms. J Biomed Biotechnol. 2010;2010:617469. doi: 10.1155/2010/617469. Epub 2010 Jun 8. PubMed PMID: 20625503; PubMed Central PMCID: PMC2896710.
  18. Scharfe C, Lu HH, Neuenburg JK, Allen EA, Li GC, Klopstock T, Cowan TM, Enns GM, Davis RW. Mapping gene associations in human mitochondria using clinical disease phenotypes. PLoS Comput Biol. 2009 Apr;5(4):e1000374. doi: 10.1371/journal.pcbi.1000374. Epub 2009 Apr 24. PubMed PMID: 19390613; PubMed Central PMCID: PMC2668170.
  19. Schrijver I, Pique LM, Traynis I, Scharfe C, Sehnert AJ. Mitochondrial DNA analysis by multiplex denaturing high-performance liquid chromatography and selective sequencing in pediatric patients with cardiomyopathy. Genet Med.2009 Feb;11(2):118-26. doi: 10.1097/GIM.0b013e318190356b. PubMed PMID: 19265752.
  20. Kivisild T, Shen P, Wall DP, Do B, Sung R, Davis K, Passarino G, Underhill PA, Scharfe C, Torroni A, Scozzari R, Modiano D, Coppa A, de Knijff P, Feldman M, Cavalli-Sforza LL, Oefner PJ. The role of selection in the evolution of human mitochondrial genomes. Genetics. 2006 Jan;172(1):373-87. doi: 10.1534/genetics.105.043901. Epub 2005 Sep 19. PubMed PMID: 16172508; PubMed Central PMCID: PMC1456165.
  21. Schmitt S, Prokisch H, Schlunck T, Camp DG 2nd, Ahting U, Waizenegger T, Scharfe C, Meitinger T, Imhof A, Neupert W, Oefner PJ, Rapaport D. Proteome analysis of mitochondrial outer membrane from Neurospora crassa. Proteomics. 2006 Jan;6(1):72-80. doi: 10.1002/pmic.200402084. PubMed PMID: 16294304.
  22. Prokisch H, Andreoli C, Ahting U, Heiss K, Ruepp A, Scharfe C, Meitinger T. MitoP2: the mitochondrial proteome database--now including mouse data. Nucleic Acids Res. 2006 Jan 1;34(Database issue):D705-11. doi: 10.1093/nar/gkj127. PubMed PMID: 16381964; PubMed Central PMCID: PMC1347489.
  23. van der Zwaag B, Burbach JP, Scharfe C, Oefner PJ, Brunner HG, Padberg GW, van Bokhoven H. Identifying new candidate genes for hereditary facial paresis on chromosome 3q21-q22 by RNA in situ hybridization in mouse.Genomics. 2005 Jul;86(1):55-67. doi: 10.1016/j.ygeno.2005.03.007. Epub 2005 Apr 20. PubMed PMID: 15953540.
  24. Prokisch H, Scharfe C, Camp DG 2nd, Xiao W, David L, Andreoli C, Monroe ME, Moore RJ, Gritsenko MA, Kozany C, Hixson KK, Mottaz HM, Zischka H, Ueffing M, Herman ZS, Davis RW, Meitinger T, Oefner PJ, Smith RD, Steinmetz LM. Integrative analysis of the mitochondrial proteome in yeast. PLoS Biol. 2004 Jun;2(6):e160. doi: 10.1371/journal.pbio.0020160. Epub 2004 Jun 15. PubMed PMID: 15208715; PubMed Central PMCID: PMC423137.
  25. Andreoli C, Prokisch H, Hörtnagel K, Mueller JC, Münsterkötter M, Scharfe C, Meitinger T. MitoP2, an integrated database on mitochondrial proteins in yeast and man. Nucleic Acids Res. 2004 Jan 1;32(Database issue):D459-62. doi: 10.1093/nar/gkh137. PubMed PMID: 14681457; PubMed Central PMCID: PMC308871.
  26. Horváth R, Lochmüller H, Scharfe C, Do BH, Oefner PJ, Müller-Höcker J, Schoser BG, Pongratz D, Auer DP, Jaksch M. A tRNA(Ala) mutation causing mitochondrial myopathy clinically resembling myotonic dystrophy. J Med Genet. 2003 Oct;40(10):752-7. doi: 10.1136/jmg.40.10.752. PubMed PMID: 14569122; PubMed Central PMCID: PMC1735288.
  27. Gu Z, Steinmetz LM, Gu X, Scharfe C, Davis RW, Li WH. Role of duplicate genes in genetic robustness against null mutations. Nature. 2003 Jan 2;421(6918):63-6. doi: 10.1038/nature01198. PubMed PMID: 12511954.
  28. Horváth R, Scharfe C, Hoeltzenbein M, Do BH, Schröder C, Warzok R, Vogelgesang S, Lochmüller H, Müller-Höcker J, Gerbitz KD, Oefner PJ, Jaksch M. Childhood onset mitochondrial myopathy and lactic acidosis caused by a stop mutation in the mitochondrial cytochrome c oxidase III gene. J Med Genet. 2002 Nov;39(11):812-6. doi: 10.1136/jmg.39.11.812. PubMed PMID: 12414820; PubMed Central PMCID: PMC1735018.
  29. Steinmetz LM, Scharfe C, Deutschbauer AM, Mokranjac D, Herman ZS, Jones T, Chu AM, Giaever G, Prokisch H, Oefner PJ, Davis RW. Systematic screen for human disease genes in yeast. Nat Genet. 2002 Aug;31(4):400-4. doi: 10.1038/ng929. Epub 2002 Jul 22. PubMed PMID: 12134146.
  30. Fraser HB, Hirsh AE, Steinmetz LM, Scharfe C, Feldman MW. Evolutionary rate in the protein interaction network.Science. 2002 Apr 26;296(5568):750-2. doi: 10.1126/science.1068696. PubMed PMID: 11976460.
  31. Jaksch M, Kleinle S, Scharfe C, Klopstock T, Pongratz D, Müller-Höcker J, Gerbitz KD, Liechti-Gallati S, Lochmuller H, Horvath R. Frequency of mitochondrial transfer RNA mutations and deletions in 225 patients presenting with respiratory chain deficiencies. J Med Genet. 2001 Oct;38(10):665-73. doi: 10.1136/jmg.38.10.665. PubMed PMID: 11584044; PubMed Central PMCID: PMC1734743.
  32. Pusch CM, Zeitz C, Brandau O, Pesch K, Achatz H, Feil S, Scharfe C, Maurer J, Jacobi FK, Pinckers A, Andreasson S, Hardcastle A, Wissinger B, Berger W, Meindl A. The complete form of X-linked congenital stationary night blindness is caused by mutations in a gene encoding a leucine-rich repeat protein. Nat Genet. 2000 Nov;26(3):324-7. doi: 10.1038/81627. PubMed PMID: 11062472.
  33. Scharfe C, Hauschild M, Klopstock T, Janssen AJ, Heidemann PH, Meitinger T, Jaksch M. A novel mutation in the thiamine responsive megaloblastic anaemia gene SLC19A2 in a patient with deficiency of respiratory chain complex I. J Med Genet. 2000 Sep;37(9):669-73. doi: 10.1136/jmg.37.9.669. PubMed PMID: 10978358; PubMed Central PMCID: PMC1734685.
  34. Scharfe C, Zaccaria P, Hoertnagel K, Jaksch M, Klopstock T, Dembowski M, Lill R, Prokisch H, Gerbitz KD, Neupert W, Mewes HW, Meitinger T. MITOP, the mitochondrial proteome database: 2000 update. Nucleic Acids Res. 2000 Jan 1;28(1):155-8. doi: 10.1093/nar/28.1.155. PubMed PMID: 10592209; PubMed Central PMCID: PMC102491.
  35. Scharfe C, Zaccaria P, Hoertnagel K, Jaksch M, Klopstock T, Lill R, Prokisch H, Gerbitz KD, Mewes HW, Meitinger T. MITOP: database for mitochondria-related proteins, genes and diseases. Nucleic Acids Res. 1999 Jan 1;27(1):153-5. doi: 10.1093/nar/27.1.153. PubMed PMID: 9847163; PubMed Central PMCID: PMC148118.
  36. Strom TM, Hörtnagel K, Hofmann S, Gekeler F, Scharfe C, Rabl W, Gerbitz KD, Meitinger T. Diabetes insipidus, diabetes mellitus, optic atrophy and deafness (DIDMOAD) caused by mutations in a novel gene (wolframin) coding for a predicted transmembrane protein. Hum Mol Genet. 1998 Dec;7(13):2021-8. doi: 10.1093/hmg/7.13.2021. PubMed PMID: 9817917.
  37. Meitinger T, Scharfe C, Call K, Moschonas N. Report of the second international workshop on human chromosome 10 mapping 1997. Cytogenet Cell Genet. 1997;78(3-4):184-94. PubMed PMID: 9465886.


Research Interests

Biotechnology; Cystic Fibrosis; DNA; DNA Virus Infections; Heart Defects, Congenital; Infant, Newborn, Diseases; Metabolism, Inborn Errors; Prenatal Diagnosis; Genomics; Molecular Diagnostic Techniques; Mitochondrial Diseases; Proteomics; Microarray Analysis; High-Throughput Nucleotide Sequencing

Selected Publications