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Damian Krysan

TitleAssociate Professor
InstitutionSchool of Medicine and Dentistry
DepartmentPediatrics
AddressUniversity of Rochester Medical Center
School of Medicine and Dentistry
601 Elmwood Ave, Box 850
Rochester NY 14642
Other Positions
TitleAssociate Professor
InstitutionSchool of Medicine and Dentistry
DepartmentMicrobiology and Immunology

 
 Awards And Honors
1999     Harry A. Towsley Award for Excellence in Pediatrics, University of Michigan
1999     Department of Pediatrics Resident Research Grant, University of Michigan
2003     NIH Pediatric Loan Repayment Program
2012     1st Tennessee Chair Distinguished Visiting Professor
2012     Ruth A. Lawrence Academic Faculty Service Award in Research
2013     Featured APS New Member of the Month
2013     Elected to American Pediatric Society
 
 Overview
Dr. Krysan's research focuses on two broad areas: 1) antifungal and antibiotic drug discovery and 2) fungal pathogenesis.

First, our antifungal and antibiotic drug discovery work involves high-throughput screening, characterizing in vitro and in vivo activity, determining mechanism of action and structure-activity optimization of new leads. We are currently studying triphenylethylene-bases molecules similar to tamoxifen as anti-cryptococcal agents, PDK1 kinase inhibitors as antifungal agents (in collaboration with Dr. Robert Boeckman from the Department of Chemistry), and a variety of new molecular scaffolds. High-throughput screening projects involve (in collaboration with Dr. Paul Dunman from the Department of Microbiology) the ESKAPE (Enterococcus, Staphylococcus, Klebsiella, Acinetobacter, Pseudomonas and Enterobacter) bacterial pathogens and Mycobacterium tuberculosis.

Second, we use large-scale genetic approaches to study the pathogenesis and host-pathogen interactions of Candida albicans, the most common human fungal pathogen. These studies are carried out in collaboration with Dr. Anuj Kumar (University of Michigan), and Dr. Melanie Wellington (University of Rochester, Pediatric Infectious Diseases). We are particularly interested in how genetic networks regulate morphogenesis and interactions with macrophages.

 
 Selected Publications
List All   |   Timeline
  1. Roemer T, Krysan DJ. Antifungal drug development: challenges, unmet clinical needs, and new approaches. Cold Spring Harb Perspect Med. 2014; 4(5).
    View in: PubMed
  2. Falsetta ML, Klein MI, Colonne PM, Scott-Anne K, Gregoire S, Pai CH, Gonzalez-Begne M, Watson G, Krysan DJ, Bowen WH, Koo H. Symbiotic Relationship between Streptococcus mutans and Candida albicans Synergizes Virulence of Plaque Biofilms In Vivo. Infect Immun. 2014 May; 82(5):1968-81.
    View in: PubMed
  3. Butts A, Koselny K, Chabrier-Roselló Y, Semighini CP, Brown JC, Wang X, Annadurai S, Didone L, Tabroff J, Childers WE, Abou-Gharbia M, Wellington M, Cardenas ME, Madhani HD, Heitman J, Krysan DJ. Estrogen Receptor Antagonists Are Anti-Cryptococcal Agents That Directly Bind EF Hand Proteins and Synergize with Fluconazole In Vivo. MBio. 2014; 5(1).
    View in: PubMed
  4. Wellington M, Koselny K, Sutterwala FS, Krysan DJ. Candida albicans Triggers NLRP3-Mediated Pyroptosis in Macrophages. Eukaryot Cell. 2014 Feb; 13(2):329-40.
    View in: PubMed
  5. Wellington M, Koselny K, Krysan DJ. Candida albicans Morphogenesis Is Not Required for Macrophage Interleukin 1ß Production. MBio. 2012; 4(1).
    View in: PubMed
  6. Butts A, Didone L, Koselny K, Baxter BK, Chabrier-Rosello Y, Wellington M, Krysan DJ. A repurposing approach identifies off-patent drugs with fungicidal cryptococcal activity, a common structural chemotype, and pharmacological properties relevant to the treatment of cryptococcosis. Eukaryot Cell. 2013 Feb; 12(2):278-87.
    View in: PubMed
  7. Chabrier-Roselló Y, Gerik KJ, Koselny K, Didone L, Lodge JK, Krysan DJ. Cryptococcus neoformans Phosphoinositide-Dependent Kinase 1 (PDK1) Ortholog Is Required for Stress Tolerance and Survival in Murine Phagocytes. Eukaryot Cell. 2013 Jan; 12(1):12-22.
    View in: PubMed
  8. Jacobs AC, Didone L, Jobson J, Sofia MK, Krysan D, Dunman PM. Adenylate kinase release as a high-throughput-screening-compatible reporter of bacterial lysis for identification of antibacterial agents. Antimicrob Agents Chemother. 2013 Jan; 57(1):26-36.
    View in: PubMed
  9. Butts A, Krysan DJ. Antifungal drug discovery: something old and something new. PLoS Pathog. 2012 Sep; 8(9):e1002870.
    View in: PubMed
  10. Saputo S, Chabrier-Rosello Y, Luca FC, Kumar A, Krysan DJ. The RAM network in pathogenic fungi. Eukaryot Cell. 2012 Jun; 11(6):708-17.
    View in: PubMed
  11. Biondi E, Krysan D. Treatment with oseltamivir decreases the length of hospital stay in critically ill children with influenza. J Pediatr. 2012 Mar; 160(3):528-9.
    View in: PubMed
  12. DiDone L, Oga D, Krysan DJ. A novel assay of biofilm antifungal activity reveals that amphotericin B and caspofungin lyse Candida albicans cells in biofilms. Yeast. 2011 Aug; 28(8):561-8.
    View in: PubMed
  13. Bharucha N, Chabrier-Rosello Y, Xu T, Johnson C, Sobczynski S, Song Q, Dobry CJ, Eckwahl MJ, Anderson CP, Benjamin AJ, Kumar A, Krysan DJ. A large-scale complex haploinsufficiency-based genetic interaction screen in Candida albicans: analysis of the RAM network during morphogenesis. PLoS Genet. 2011 Apr; 7(4):e1002058.
    View in: PubMed
  14. Kainth MK, Krysan DJ. Age and symptoms affect the prevalence of group A beta-hemolytic streptococcus in pharyngeal cultures of school-age children. J Pediatr. 2011 Mar; 158(3):515-6.
    View in: PubMed
  15. Baxter BK, DiDone L, Ogu D, Schor S, Krysan DJ. Identification, in vitro activity and mode of action of phosphoinositide-dependent-1 kinase inhibitors as antifungal molecules. ACS Chem Biol. 2011 May 20; 6(5):502-10.
    View in: PubMed
  16. Miller KA, DiDone L, Krysan DJ. Extracellular secretion of overexpressed glycosylphosphatidylinositol-linked cell wall protein Utr2/Crh2p as a novel protein quality control mechanism in Saccharomyces cerevisiae. Eukaryot Cell. 2010 Nov; 9(11):1669-79.
    View in: PubMed
  17. DiDone L, Scrimale T, Baxter BK, Krysan DJ. A high-throughput assay of yeast cell lysis for drug discovery and genetic analysis. Nat Protoc. 2010 Jun; 5(6):1107-14.
    View in: PubMed
  18. Dolan K, Montgomery S, Buchheit B, Didone L, Wellington M, Krysan DJ. Antifungal activity of tamoxifen: in vitro and in vivo activities and mechanistic characterization. Antimicrob Agents Chemother. 2009 Aug; 53(8):3337-46.
    View in: PubMed
  19. Krysan DJ. The cell wall and endoplasmic reticulum stress responses are coordinately regulated in Saccharomyces cerevisiae. Commun Integr Biol. 2009 May; 2(3):233-5.
    View in: PubMed
  20. Krysan D. Serum procalcitonin levels aid in distinguishing bacterial from aseptic meningitis in children. J Pediatr. 2009 May; 154(5):773.
    View in: PubMed
  21. Wellington M, Dolan K, Krysan DJ. Live Candida albicans suppresses production of reactive oxygen species in phagocytes. Infect Immun. 2009 Jan; 77(1):405-13.
    View in: PubMed
  22. Scrimale T, Didone L, de Mesy Bentley KL, Krysan DJ. The unfolded protein response is induced by the cell wall integrity mitogen-activated protein kinase signaling cascade and is required for cell wall integrity in Saccharomyces cerevisiae. Mol Biol Cell. 2009 Jan; 20(1):164-75.
    View in: PubMed
  23. Krysan DJ, Didone L. A high-throughput screening assay for small molecules that disrupt yeast cell integrity. J Biomol Screen. 2008 Aug; 13(7):657-64.
    View in: PubMed
  24. Vadaie N, Dionne H, Akajagbor DS, Nickerson SR, Krysan DJ, Cullen PJ. Cleavage of the signaling mucin Msb2 by the aspartyl protease Yps1 is required for MAPK activation in yeast. J Cell Biol. 2008 Jun 30; 181(7):1073-81.
    View in: PubMed
  25. Ma J, Dobry CJ, Krysan DJ, Kumar A. Unconventional genomic architecture in the budding yeast saccharomyces cerevisiae masks the nested antisense gene NAG1. Eukaryot Cell. 2008 Aug; 7(8):1289-98.
    View in: PubMed
  26. Krysan DJ, Ting EL, Abeijon C, Kroos L, Fuller RS. Yapsins are a family of aspartyl proteases required for cell wall integrity in Saccharomyces cerevisiae. Eukaryot Cell. 2005 Aug; 4(8):1364-74.
    View in: PubMed
  27. Krysan DJ. Effectiveness over time of varicella vaccine. J Pediatr. 2004 Sep; 145(3):416-7.
    View in: PubMed
  28. Rozan L, Krysan DJ, Rockwell NC, Fuller RS. Plasticity of extended subsites facilitates divergent substrate recognition by Kex2 and furin. J Biol Chem. 2004 Aug 20; 279(34):35656-63.
    View in: PubMed
  29. Krysan D. Effectiveness of inactivated influenza vaccine in preventing acute otitis media in young children: a randomized controlled trial. J Pediatr. 2004 Mar; 144(3):406-7.
    View in: PubMed
  30. Rockwell NC, Krysan DJ, Komiyama T, Fuller RS. Precursor processing by kex2/furin proteases. Chem Rev. 2002 Dec; 102(12):4525-48.
    View in: PubMed
  31. Krysan DJ, Kemper AR. Claims of equivalence in randomized controlled trials of the treatment of bacterial meningitis in children. Pediatr Infect Dis J. 2002 Aug; 21(8):753-8.
    View in: PubMed
  32. Kemper AR, Krysan DJ. Reevaluating the efficacy of naturopathic ear drops. Arch Pediatr Adolesc Med. 2002 Jan; 156(1):88-9.
    View in: PubMed
  33. Krysan DJ, Flynn JT. Renal transplantation after Streptococcus pneumoniae-associated hemolytic uremic syndrome. Am J Kidney Dis. 2001 Feb; 37(2):E15.
    View in: PubMed
  34. Rockwell NC, Krysan DJ, Fuller RS. Synthesis of peptidyl methylcoumarin esters as substrates and active-site titrants for the prohormone processing proteases Kex2 and PC2. Anal Biochem. 2000 May 1; 280(2):201-8.
    View in: PubMed
  35. Krysan DJ, Rockwell NC, Fuller RS. Quantitative characterization of furin specificity. Energetics of substrate discrimination using an internally consistent set of hexapeptidyl methylcoumarinamides. J Biol Chem. 1999 Aug 13; 274(33):23229-34.
    View in: PubMed
  36. Krysan DJ, Mackenzie PB. Optically active 2-ethenyl-1,3-dioxolanones as 3-carbon synthons. Allylnickel derivatives as homoenolate equivalents. J Am Chem Soc. 1988 Aug 1; 110(18):6273-4.
    View in: PubMed

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