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Dawit Kidane-Mulat
Faculty
Faculty

Dawit Kidane-Mulat, Ph.D. DABT (Board Certified Toxicologist)

Associate Professor

  • Physiology & Biophysics
  • College of Medicine

Biography

Most cancers treated with targeted therapy ultimately become resistant to treatment, stop shrinking, and eventually progress. Based on the improved understanding of the mechanisms on cancer initiation, promotion and progression model, targeted therapies are emerging as groundbreaking and promising treatment strategies. Dr. Kidane lab uses genetic tools, cancer genomics and metabolomics data approaches to uncover basic mechanism of genomic instability and cancer. Moreover, Dr. Kidane lab developed genetic tools including animal and in vitro models to uncover mechanistic insight how DNA repair deficiency induces innate immune response and inflammation, and applied systems biology approaches to understand the activation and regulation of innate immune signaling. His research program prioritizes pre-clinical research with strong clinical/translational relevance with an emphasis on tumor immunology in gastrointestinal cancer including stomach, colon, and pancreatic cancer. More specific areas of research interest include: -

  • Oxidative DNA damage and repair
  • DNA replication stress
  • Targeting DNA repair deficiency in cancer therapy.
  • Exploring DNA repair deficiency to elicit inflammatory signaling and enhance immunotherapy.
  • Manipulating cancer cells metabolic demand to promote better treatment response.

Kidane Lab

 

 

 

 

 

Education & Expertise

Education

Ph.D.

Genetics
Albert-Ludwig University of Freiburg, Germany

Postdoctoral Fellow


Yale School of Medicine, Therapeutic Radiology and Human Genetics
2007-2011

Expertise

Cancer Genetics &Genomics

  • DNA Damage & Repair
  • DNA repair targeted therapy  

Tumor Immunology

  • Innate immune signaling, Inflammation &Cancer 

Research

Research

Specialty

DNA Damage, Repair and Cancer

Funding

NIH/NCI  (R21)

Dawit Kidane-Mulat (PI)           04/01/2021 – 07/31/2024     

Title: The Role of Base Excision Repair in Regulating DNA-Mediated Inflammatory Signaling Pathways

American Gastroenterological Association. Robert & Sally Funderburg Research Award

Dawit Kidane-Mulat (PI)   01/01/21-11/30/24   

Title: Mechanisms of Base Excision Repair and Gastric Cancer.

DeGregorio Family Foundation Research Award    

Dawit Kidane-Mulat  (PI)   01/15/2022-12/30/2024

Title: Harnessing DNA Damage Response to Enhance Immunotherapy Response in XRCC1 Deficient Stomach Cancer.

NIH/NIAID: 1R01AI179899-01

Dawit Kidane-Mulat  (PI)  12/08/2023-11/30/2028

Title: Linking defects in DNA polymerase beta to mitochondrial dysfunction and cytosolic nucleic acid sensor in Helicobacter pylori associated inflammation.

Group Information

Lab Membres 

Aashirwad Shahi, Ph.D.  Postdoctoral Associate

Brutha Khushi , Lab manager

Barry Cristofer, MD student

Nakiah Gipson, MD student, Summer research fellow

Ah'mari Jones, Undergarduate (Biology)

Yem Nguimbous , Undergarduate (Biology)

 

Coming Soon!

Graduate students

I am looking for PhD students to start in fall 2024. If you are interested in working on cancer etiology and looking for therapeutic strategy, you may be a good fit in our lab. In all cases, I encourage my students to find, design, and execute their research on their own, with me as a collaborator. I believe this approach helps them to become independent and creative scientists.

Undergraduate students/Medical students

Students are welcome to participate in the research conducted in our lab throughout the year. 

Postdoctoral fellows

Position available.  Welcome inquiries regarding postdoc possibilities in our lab.

Lab Manger/Lab tech

Position available

 Join the lab! 

Accomplishments

Accomplishments

  • Anna Fuller Postdoctoral Fellowship in Molecular Oncology, Yale School of Medicine
  • Pfizer Award for Excellence in Research
  • Ellison Medical Foundation Scholarship Award
  •  Keystone Symposia Scholarship Award from the National Institute of Aging on Genomic Instability and Repair
  • Infectious Disease Research Recognition Award from Centers of Disease Control
  • WHO/TDR Training Grant Award for Genomics and Bioinformatics
  • WHO/TDR Training Grant Award for Immunology and Vaccinology

 

Related Articles

PEER-REVIEWED PUBLICATIONS

Barry Cristofer,  Aashirwad Shahi  and  Kidane.D. *DNA glycosylase (NEIL3) overexpression associated with low tumor immune infiltration and poor overall patient survival in endometrial cancer. OncoImmunology (in-press), 2024.* represent corresponding author. 

Aashirwad Shahi and  Kidane.D*. Decoding mitochondria DNA damage and repair associated with H. pylori infection. Critical Review in Microbiology (in-press) , 2024.* represent corresponding author. 

Aashirwad Shahi and Kidane, D.* Starving cancer cells to enhances DNA damage and immunotherapy response. Oncotraget 2024. PMID: 38900609 ;https://doi.org/10.18632/oncotarget.28595.* represent corresponding author. 

Zackary Shpilman and Kidane, D* Dysregulation of base excision repair factors associated with low tumor immunogenicity in head and neck cancer: implication for immunotherapy. Therapeutic Advances in Medical Oncology, 2024: 16:17588359241248330. PMID: 38680291 PMCID: PMC11047243. https://doi.org/10.1177/17588359241248330.  * represent corresponding author.

Vidhyanand Mahase , Adebiyi Sobitan , Qiaobin Yao, Xinghua Shi, Hong Qin , Kidane, D, Qiyi Tang and Shaolei Teng.  Impact of Missense Mutations on Spike Protein Stability and Binding Affinity in the Omicron Variant. Viruses 2024, 16(7), 1150; https://doi.org/10.3390/v16071150

Shahi, A and Kidane, D.* Aberrant DNA polymerase beta expression is associated with dysregulated tumor immune microenvironment in gastric cancer. Clin Exp Med. 2024 Oct 14;24(1):239. doi: 10.1007/s10238-024-01498-7 PMID: 39402431.* represent corresponding author.

Zhao S, Francois. and Kidane, D*. Inhibition of DHODH Enhances Replication-Associated Genomic Instability and Promotes Sensitivity in Endometrial Cancer. Cancers .2023 Dec 6;15(24):5727.PMID: 38136273 PMCID: PMC10741824 doi:10.3390/cancers15245727. * represent corresponding author 

Saha,A.,  Zhao,S.,  Austin Kindall, Carly WilderChelsea A. Friedman, Rachel Clark, George Georgiou, Everett Stone,  Kidane, D*, John DiGiovanni* . Cysteine Depletion Sensitizes Prostate Cancer Cells to Agents that Enhance DNA Damage and to Immune Checkpoint Inhibition. J Exp Clin Cancer Res. 2023 ;42(1):119. PMID: 37170264; PMCID: PMC10173527; DOI: 10.1186/s13046-023-02677-2.  * represent corresponding author

Zhao, S.; Julia A. Goewey Ruiz; Sebastian, M.; Kidane, D*. DNA Polymerase beta  defects invokes cGAS/STING mediated innate immune signaling and promotes an inflammatory response. Front Immunol. 2022:13:1039009. PMID: 36624848; PMCID: PMC9823925   DOI: 10.3389/fimmu.2022.1039009. eCollection 2022.  * represent corresponding author

Zhao, S.; Habib, S.L.; Senejani, A.G.; Sebastian, M.; Kidane, D*. Role of Base Excision Repair in Innate Immune Cells and Its Relevance for Cancer Therapy. Biomedicines 2022, 10, 557. PMID: 35327359; PMCID: PMC8945362: DOI: 10.3390/biomedicines10030557.* represent corresponding author

Saha A, Zhao S, Chen Z, Georgiou G, Stone E, Kidane D*, DiGiovanni J. Combinatorial Approaches to Enhance DNA Damage Following Enzyme-mediated Depletion of L-Cys for Treatment of Pancreatic Cancer. Molecular Therapy Feb 2021;29(2):775-787. PMID: 33091613. PMCID: PMC7854304. DOI: 10.1016/j.ymthe.2020.10.016. * represent corresponding author

Zhao S, Devega R, Francois A, Kidane D*. Human ALKBH6 Is Required for Maintenance of Genomic Stability and Promoting Cell Survival During Exposure of Alkylating Agents in Pancreatic Cancer. Frontiers in Genetics April 2021; 12:635808. PMID: 33897761. DOI: 10.3389/fgene.2021.635808. * represent corresponding author

Tran OT, Tadesse S, Chu C, Kidane D*. Overexpression of NEIL3 associated with altered genome and poor survival in selected types of human cancer. Tumor Biology May 2020; 42(5):1010428320918404. PMID: 32364878. DOI: 10.1177/1010428320918404

Zhao S, Thakur M, Klattenhoff AW, Kidane D*. Aberrant DNA Polymerase Beta Enhances H. pylori Infection Induced Genomic Instability and Gastric Carcinogenesis in Mice. Cancers (Basel) June 2019;11(6):843. PMID: 31216714. DOI: 10.3390/cancers11060843

Zhao S, Klattenhoff AW, Thakur M, Sebastian M, Kidane D*. Mutation in DNA polymerase beta causes chromosomal instability and inflammation-associated carcinogenesis in mice. Cancers (Basel) Aug 2019;11(8):1160. PMID: 31412651. DOI: 10.3390/cancers11081160. * represent corresponding author

Kidane D*. Mechanism of H. pylori- induced DNA double-strand breaks. International Journal of Molecular Sciences Sept 2018;19(10):2891. PMCID: PMC6213211. DOI: 10.3390/ijms19102891. * represent corresponding author

Klattenhoff AW, Thakur M, Chu SC, Ray D, Habib SL, Kidane D*. Loss of NEIL3 DNA glycosylase markedly increases replication associated double strand breaks and enhances sensitivity to ATR inhibition in glioblastoma cells. Oncotarget Dec 2017;8(68):112942-112958. PMID: 29348879. DOI: 10.18632/oncotarget.22896. * represent corresponding author

Ray D, Kidane D*. Gut Microbiota imbalance and base excision repair dynamics in colon cancer. Journal of Cancer Jul 2016;7(11):1421-1430. PMID: 27471558. DOI: 10.7150/jca.15480.* represent corresponding author

Tadesse S, Norwitz NG, Guller S, Arcuri F, Toti P, Norwitz ER, Kidane D*. Dynamics of base excision repair at the maternal-fetal interface in pregnancies complicated by preeclampsia. Reproductive Sciences Jun 2017;24(6):856-864. PMID: 27707956. DOI: 10.1177/1933719116670519.* represent corresponding author

Habib SL, Yadav A, Kidane D, Weiss RH, Liang S. Novel protective mechanism of reducing renal cell damage in diabetes: Activation AMPK by AICAR increased NRF2/OGG1 proteins and reduced oxidative DNA damage. Cell Cycle Nov 2016 Nov;15(22):3048-3059. PMID: 27611085. DOI: 10.1080/15384101.2016.1231259

Rozacky J, Nemec AA, Sweasy JB, Kidane D*. Gastric cancer associated variant of DNA polymerase beta (Leu22Pro) promotes DNA replication associated double strand breaks. Oncotarget Sep 2015;6(27):24474-87. PMID: 26090616. DOI: 10.18632/oncotarget.4426. * represent corresponding author

Kidane, D*, Murphy DL, Sweasy JB. Accumulation of abasic sites induces genomic instability in normal human gastric epithelial cells during Helicobacter pylori infection. Oncogenesis Nov 2014;3(11):e128. PMID: 25417725. DOI: 10.1038/oncsis.2014.42.  * represent corresponding author

Tadesse S, Kidane D, Guller S, Luo T, Norwitz NG, Arcuri F, Toti P, Norwitz ER. In vivo and in vitro evidence for placental DNA damage in preeclampsia. PLOS ONE Jan 2014;9(1):e86791. PMID: 24466242. DOI: 10.1371/journal.pone.0086791

 Kidane D, Chae WJ, Czochor J, Eckert KA, Glazer PM, Bothwell AL, Sweasy JB. Interplay between DNA repair and inflammation, and the link to Cancer. Critical Reviews in Biochemistry and Molecular Biology Mar-Apr 2014;49(2):116-39. PMID 24410153. DOI: 10.3109/10409238.2013.875514

Senejani AG, Liu Y, Kidane D, Maher SE, Zeiss CJ, Park HJ, Kashgarian M, McNiff JM, Zelterman D, Bothwell AL, Sweasy JB. Mutation of POLB causes lupus in mice. Cell Reports Jan 2014;6(1):1-8. PMID: 24388753. DOI: 10.1016/j.celrep.2013.12.017

Galick HA, Kathe S, Liu M, Robey-Bond S, Kidane D, Wallace SS, Sweasy JB. Germ-line variant of human NTH1 DNA glycosylase induces genomic instability and cellular transformation. Proceedings of the National Academy of Sciences of the United States of America Aug 2013;110(35):14314-9. PMID: 23940330. DOI: 10.1073/pnas.1306752110

Kidane D, Sakkas D, Nottoli T, McGrath J, Sweasy JB. Kinesin 5B (KIF5B) is required for progression through female meiosis and proper chromosomal segregation in mitotic cells. PLOS ONE Apr 2013;8(4):e58585. PMID: 23560038. DOI: 10.1371/journal.pone.0058585

Kidane D, Ayora S, Sweasy JB, Graumann PL, Alonso JC. The cell pole: the site of cross talk between the DNA uptake and genetic recombination machinery. Critical Reviews in Biochemistry and Molecular Biology Nov-Dec 2012;47(6):531-55. PMID: 23046409. DOI: 10.3109/10409238.2012.729562

Kidane D, Sweasy JB. Tipping the balance the powerhouse of Cell to “protect” colorectal cancer. PLOS Genetics Jun 2012;8(6):e1002758. PMID: 22685422. DOI: 10.1371/journal.pgen.1002758

Kidane D, Dala S, Keh A, Liu Y, Zelterman D, Sweasy JB. DNA polymerase beta is critical for genomic stability of sperm cells. DNA Repair Apr 2011;10(4):390-7. PMID: 21333614. DOI: 10.1016/j.dnarep.2011.01.003

Kidane D, Jonason AS, Gorton TS, Mihaylov I, Pan J, Keeney S, de Rooij DG, Ashley T, Keh A, Liu Y, Banerjee U, Zelterman D, Sweasy JB. DNA Polymerase beta is critical for mouse meiotic synapsis. EMBO Journal Jan 2010;29(2):410-23. PMID: 20019666. DOI: 10.1038/emboj.2009.357

Kidane D, Carrasco B, Manfredi C, Rothmaier K, Ayora S, Tadesse S, Alonso JC, Graumann PL. Evidence for different pathways during horizontal gene transfer in competent Bacillus subtilis cells. PLOS Genetics Sep 2009;5(9):e1000630. PMID: 19730681. DOI: 10.1371/journal.pgen.1000630

Mascarenhas J, Sanchez H, Tadesse S, Kidane D, Krishnamurthy M, Alonso JC, Graumann PL. Bacillus subtilis SbcC protein plays an important role in DNA inter-strand cross-link repair. BMC Molecular Biology Jun 2006;7-20. PMID: 16780573. DOI: 10.1186/1471-2199-7-20

Genetu A, Gadisa E, Aseffa A, Barr S, Lakew M, Jirata D, Kuru T, Kidane D, Hunegnaw M, Gedamu L. Leishmania aethiopica: Strain identification and characterization of superoxide dismutase-B genes. Experimental Parasitology Aug 2006;113(4):221-226. PMID: 16516199. DOI: 10.1016/j.exppara.2006.01.010

Sanchez H, Kidane D, Castillo Cozar M, Graumann PL, Alonso JC. Recruitment of Bacillus subtilis RecN to DNA double-strand breaks in the absence of DNA end processing. Journal of Bacteriology Jan 2006;188(2):353-360. PMID: 16385024. DOI: 10.1128/JB.188.2.353-360.2006

Kidane D, Graumann PL. Dynamic formation of RecA filaments at DNA double strand repair centers in live cells. Journal of Cell Biology Aug 2005;170(3):357-366. PMID: 16061691. DOI: 10.1083/jcb.200412090

Sanchez H, Kidane D, Reed P, Curtis FA, Castillo Cozar M, Graumann PL, Sharples GJ, Alonso JC. The RuvAB branch migration translocase and RecU Holliday junction resolvase are required for double-stranded DNA break repair in Bacillus subtilis. Genetics Nov 2005;171(3):873-883. PMID: 16020779. DOI: 10.1534/genetics.105.045906

Kidane D, Graumann PL. Intracellular protein and DNA dynamics in competent Bacillus subtilis cells. Cell Jul 2005;122(1):73-84. PMID: 16009134. DOI: 10.1016/j.cell.2005.04.036

Kidane D, Sanchez H, Alonso JC, Graumann PL. Visualization of DNA double-strand break repair in live bacteria reveals dynamic recruitment of Bacillus subtilis RecF, RecO and RecN proteins to distinct sites on the nucleoids. Molecular Microbiology Jun 2004;52(6):1627-1639. PMID: 15186413. DOI: 10.1111/j.1365-2958.2004.04102.x

Habte A, Geletu M, Olobo JO, Kidane D, Negesse Y, Yassin MA, Kifle A, Abate G, Harboe M,  Aseffa A. T cell mediated immune responses in patients with tuberculosis lymphadenitis from Butajira, southern Ethiopia. Ethiopian Medical Journal Apr 2004;(42) Suppl 1:29-35. PMID: 1689501

Abebe M, Lakew M, Kidane D, Lakew Z, Kiros K, Harboe M. Female genital tuberculosis in Ethiopia. Ethiopian Medical Journal Apr 42 Suppl 1:37-41. PMID: 16895018.

Tadesse S, Woldemeskel M, Molla B, Tibbo M, Kidane D, Medhin G, Britton S. Avian mycobacteriosis in domestic chickens from selected agro-climatic regions of Ethiopia. Journal of Applied Research in Veterinary Medicine 2003;2(1):17-25.

Beyene D, Aseffa A, Harboe M, Kidane D, Macdonald M, Klatser PR, Bjune GA, Smith WC. Nasal carriage of Mycobacterium leprae DNA in healthy individuals in Lega Robi village, Ethiopia. Epidemiology and Infection Oct 2003;131(2):841-848. PMID: 14596524. DOI: 10.1017/s0950268803001079

Yassin MA, Olobo JO, Kidane D, Negesse Y, Shimeles E, Tadesse A, Demissie A, Britton S, Harboe M, Aseffa A, Abate G. Diagnosis of tuberculosis lymphadenitis in Butajira, rural Ethiopia. Scandinavian Journal of Infectious Diseases 2003;35(4):240-243. PMID: 12839151. DOI: 10.1080/00365540310004027

Kidane D, Olobo JO, Habte A, Negesse Y, Aseffa A, Abate G, Yassin MA, Bereda K, Harboe M. Identification of the causative organism of tuberculosis lymphadenitis in Ethiopia by PCR. Journal of Clinical Microbiology Nov 2002;40(11):4230-4234. PMID: 12409403. DOI: 10.1128/JCM.40.11.4230-4234.2002

 Book Chapters

Shengyuan Zhao, Tadesse S, and Kidane D*. Significance of Base Excision Repair to human health. Int Rev Cell Mol Biol. 2021; 364:163-193. PMID: 34507783 DOI: 10.1016/bs.ircmb.2021.05.002.* represent corresponding author