Prof. Nir Osherov

Full Professor, Sackler Faculty of Medicine

Chair, M.Sc. Committee, Sackler School of Medicine

Education

Human Mold Infections

Aspergillus fumigatus is the most common mold pathogen of human beings, causing invasive diseases in immunocompromised (cancer after chemotherapy, bone marrow transplant etc) patients. Poor diagnostic tools and the ineffectiveness of antifungal drugs against established Aspergillus infections combine to result in high mortality following A. fumigatus infection. Left untreated, mortality rates from invasive pulmonary aspergillosis (IPA) exceed 90% and even following aggressive antifungal treatment fatality rates of 50-70% are common.

The goals of my lab are:

• To understand what enables this mold to be such an effective and dangerous pathogen of immunocompromised patients
• To develop novel modes of treatment including new antifungal compounds, targeted antibodies and nano medicines.

1: Orasch T, Dietl AM, Shadkchan Y, Binder U, Bauer I, Lass-Flörl C, Osherov N, Haas H. The leucine biosynthetic pathway is crucial for adaptation to iron starvation and virulence in Aspergillus fumigatus. Virulence. 2019Dec;10(1):925-934

2: Raffa N, Osherov N, Keller NP. Copper Utilization, Regulation, and Acquisition by Aspergillus fumigatus. Int J Mol Sci. 2019 Apr 23;20(8).

3: Dietl AM, Binder U, Shadkchan Y, Osherov N, Haas H. Siroheme Is Essential for Assimilation of Nitrate and Sulfate as Well as Detoxification of Nitric Oxide but Dispensable for Murine Virulence of Aspergillus fumigatus. Front Microbiol. 2018 Nov 12;9:2615.

4: Dietl AM, Meir Z, Shadkchan Y, Osherov N, Haas H. Riboflavin and pantothenic acid biosynthesis are crucial for iron homeostasis and virulence in the pathogenic mold Aspergillus fumigatus. Virulence. 2018;9(1):1036-1049.

5: Yang K, Shadkchan Y, Tannous J, Landero Figueroa JA, Wiemann P, Osherov N, Wang S, Keller NP. Contribution of ATPase copper transporters in animal but not plant virulence of the crossover pathogen Aspergillus flavus. Virulence.2018;9(1):1273-1286

6: Meir Z, Osherov N. Vitamin Biosynthesis as an Antifungal Target. J Fungi (Basel). 2018 Jun 17;4(2).

7: Bertuzzi M, Hayes GE, Icheoku UJ, van Rhijn N, Denning DW, Osherov N, Bignell EM. Anti-Aspergillus Activities of the Respiratory Epithelium in Health and Disease. J Fungi (Basel). 2018 Jan 8;4(1).

8: Shemesh E, Hanf B, Hagag S, Attias S, Shadkchan Y, Fichtman B, Harel A, Krüger T, Brakhage AA, Kniemeyer O, Osherov N. Phenotypic and Proteomic Analysis of the  Aspergillus fumigatus ΔPrtT, ΔXprG and ΔXprG/ΔPrtT Protease-Deficient Mutants.Front Microbiol. 2017 Dec 12;8:2490.

9: Wiemann P, Perevitsky A, Lim FY, Shadkchan Y, Knox BP, Landero Figueora JA, Choera T, Niu M, Steinberger AJ, Wüthrich M, Idol RA, Klein BS, Dinauer MC, Huttenlocher A, Osherov N, Keller NP. Aspergillus fumigatus Copper Export Machinery and Reactive Oxygen Intermediate Defense Counter Host Copper-MediatedOxidative Antimicrobial Offense. Cell Rep. 2017 Jun 6;19(10):2174-2176.

10: Ben Yaakov D, Shadkchan Y, Albert N, Kontoyiannis DP, Osherov N. The quinoline bromoquinol exhibits broad-spectrum antifungal activity and induces oxidative stress and apoptosis in Aspergillus fumigatus. J Antimicrob Chemother. 2017 Aug 1;72(8):2263-2272.

12: Vitenshtein A, Charpak-Amikam Y, Yamin R, Bauman Y, Isaacson B, Stein N, Berhani O, Dassa L, Gamliel M, Gur C, Glasner A, Gomez C, Ben-Ami R, Osherov N, Cormack BP, Mandelboim O. NK Cell Recognition of Candida glabrata through Binding of NKp46 and NCR1 to Fungal Ligands Epa1, Epa6, and Epa7. Cell Host Microbe. 2016Oct 12;20(4):527-534

13: Osherov N, Kontoyiannis DP. The anti-Aspergillus drug pipeline: Is the glass  half full or empty? Med Mycol. 2017 Jan 1;55(1):118-124. Epub 2016 Aug 25.Review.

14: Osherov N, Ben-Ami R. Correction: Modulation of Host Angiogenesis as a Microbial Survival Strategy and Therapeutic Target. PLoS Pathog. 2016 Aug 17;12(8):e1005838.

15: Kaltdorf M, Srivastava M, Gupta SK, Liang C, Binder J, Dietl AM, Meir Z, Haas H, Osherov N, Krappmann S, Dandekar T. Systematic Identification of Anti-Fungal Drug Targets by a Metabolic Network Approach. Front Mol Biosci. 2016 Jun 17;3:22.

16: Osherov N, Ben-Ami R. Modulation of Host Angiogenesis as a Microbial Survival Strategy and Therapeutic Target. PLoS Pathog. 2016 Apr 14;12(4):e1005479.

17: Vaknin Y, Hillmann F, Iannitti R, Ben Baruch N, Sandovsky-Losica H, Shadkchan Y, Romani L, Brakhage A, Kniemeyer O, Osherov N. Identification and Characterization of a Novel Aspergillus fumigatus Rhomboid Family Putative Protease, RbdA, Involved in Hypoxia Sensing and Virulence. Infect Immun. 2016 May24;84(6):1866-1878.

18: Hover T, Maya T, Ron S, Sandovsky H, Shadkchan Y, Kijner N, Mitiagin Y, Fichtman B, Harel A, Shanks RM, Bruna RE, García-Véscovi E, Osherov N. Mechanisms of Bacterial (Serratia marcescens) Attachment to, Migration along, and Killing of Fungal Hyphae. Appl Environ Microbiol. 2016 Apr 18;82(9):2585-94.

19: Halperin A, Shadkchan Y, Pisarevsky E, Szpilman AM, Sandovsky H, Osherov N, Benhar I. Novel Water-Soluble Amphotericin B-PEG Conjugates with Low Toxicity and Potent in Vivo Efficacy. J Med Chem. 2016 Feb 11;59(3):1197-206.

20: Ben Yaakov D, Rivkin A, Mircus G, Albert N, Dietl AM, Kovalerchick D, Carmeli S, Haas H, Kontoyiannis DP, Osherov N. Identification and characterization of haemofungin, a novel antifungal compound that inhibits the final step of haem biosynthesis. J Antimicrob Chemother. 2016 Apr;71(4):946-52.

21: Mircus G, Albert N, Ben-Yaakov D, Chikvashvili D, Shadkchan Y, Kontoyiannis DP, Osherov N. Identification and characterization of a novel family of selective antifungal compounds (CANBEFs) that interfere with fungal protein synthesis. Antimicrob Agents Chemother. 2015 Sep;59(9):5631-40

Grants

2018-2022                  ISF Kamin Grant

2018-2021                   ISF Israel China Grant