Alessandro Vindigni, Ph.D.

Professor
Internal Medicine
Oncology

Cancer Biology Program
Molecular Cell Biology Program
Molecular Genetics and Genomics Program

  • 314-273-8612

  • 314-362-9221

  • 8125

  • CSRB building, 8th floor, Rooms 8844-8848

  • avindigni@wustl.edu

  • https://vindignilab.wustl.edu

  • @VindigniLab

  • genome stability, DNA repair, DNA replication, chemotherapy response, cancer etiology

  • DNA replication and repair, and the roles of these pathways on cancer initiation, progression and response to chemotherapy and immunotherapy

Research Abstract:

Our laboratory focuses on DNA replication and repair, and the roles of these pathways on cancer initiation, progression and response to chemotherapy and immunotherapy. We utilize a unique combination of biochemical, cellular, and electron microscopy approaches to study replication perturbations at single molecule resolutions. Combining these technologies, we have identified key pathways by which cancer cells respond to DNA damaging chemotherapy and have provided new insights on how to target these pathways to increase chemotherapeutic sensitivity.

We also are part of the newly established Siteman Center for Genome Integrity that fosters interactions between clinical and basic science investigators interested in genome integrity and DNA repair: https://siteman.wustl.edu/research/center-for-genome-integrity/

Ongoing projects:
1. Replication fork protection and recovery following DNA damaging chemotherapy
2. Mechanisms of chemotherapy resistance in homologous recombination deficient tumors
3. Connecting DNA replication fork instability with novel chemotherapeutic strategies for breast cancer
3. Adaptive response to chemotherapeutics
4. Role of the DNA damage response in normal and malignant hematopoietic cells
5. Connecting R-loop formation with chemotherapy response

Mentorship and Commitment to Diversity Statement:
Our lab is proud to be composed of a diverse community of scientists fascinated by the mechanisms that connect DNA and people together! We have trained 15 graduate students, 17 postdoctoral researchers, and over 25 undergraduate students from different nationalities and underrepresented minorities. In addition to our commitment to team science, we have a genuine interest in welcoming folks with diverse backgrounds and perspectives with the goal of fostering everyone's individual growth.

Selected Publications:

Tirman S, Quinet A, Wood M, Meroni A, Cybulla E, Jackson J, Pegoraro S, Simoneau A, Zou L, Vindigni A. Temporally distinct post-replicative repair mechanisms fill PRIMPOL-dependent ssDNA gaps in human cells. Mol. Cell 2021 Oct 7;81(19):4026-4040.e8. PMID: 34624216.

Tsao N, Brickner JR, Rodell R, Ganguly A, Wood M, Oyeniran C, Ahmad T, Sun H, Bacolla A, Zhang L, Lukinović V, Soll JM, Townley BA, Casanova AG, Tainer JA, He C, Vindigni A, Reynoird N, Mosammaparast N. Aberrant RNA methylation triggers recruitment of an alkylation repair complex. Mol. Cell 2021 Oct 21;81(20):4228-4242.e8. PMID: 34686315.

Graziano S, Coll-Bonfill N, Teodoro-Castro B, Kuppa S, Jackson J, Shashkova E, Mahajan U, Vindigni A, Antony E, Gonzalo S. Lamin-A/C recruits ssDNA protective proteins RPA and RAD51 to stalled replication forks to maintain fork stability. J Biol Chem. 2021 Oct 11:101301. PMID: 34648766.

Krishnamoorthy A, Jackson J, Mohamed T, Adolph M, Vindigni A, Cortez D. RADX prevents genome instability by confining replication fork reversal to stalled replication forks.
Mol. Cell 2021 Jul 15;81(14):3007-3017.e5. PMID: 34107305.

Quinet A, Tirman S, Cybulla E, Meroni A, Vindigni A. To skip or not to skip: choosing repriming to tolerate DNA damage.
Mol. Cell 2021 Feb 18;81(4):649-658. PMID: 33515486.

Gupta VG, Hirst J, Petersen S, Roby KF, Kusch M, Zhou H, Clive ML, Jewell A, Pathak HB, Godwin AK, Wilson AJ, Crispens MA, Cybulla E, Vindigni A, Fuh KC, Khabele D. Entinostat, a selective HDAC1/2 inhibitor, potentiates the effects of olaparib in homologous recombination proficient ovarian cancer.
Gynecol. Oncol. 2021 Apr 15:S0090-8258(21)00325-5. PMID: 33867143.

Genois MM, Gagné JP, Yasuhara T, Jackson J, Saxena S, Langelier MF, Ahel I, Bedford MT, Pascal JM, Vindigni A, Poirier GG, Zou L. CARM1 regulates replication fork speed and stress response by stimulating PARP1.
Mol. Cell. 2021 Feb 18;81(4):784-800.e8. PMID: 33412112.

Vessoni AT, Zhang T, Quinet A, Jeong HC, Munroe M, Wood M, Tedone E, Vindigni A, Shay JW, Greenberg RA, Batista LFZ. Telomere erosion in human pluripotent stem cells leads to ATR-mediated mitotic catastrophe.
J. Cell. Biol. 2021 Jun 7;220(6):e202011014. PMID: 33851958.

Tirman S, Cybulla E, Quinet A, Meroni A, Vindigni A. PRIMPOL ready, set, reprime! Crit. Rev. Biochem.
Mol. Biol. 2021 Feb;56(1):17-30. PMID: 33179522.

Wood M, Quinet A, Lin YL, Davis AA, Pasero P, Ayala YM, Vindigni A. TDP-43 dysfunction results in R-loop accumulation and DNA replication defects.
J. Cell Sci. 2020 Oct 30;133(20):jcs244129. PMID: 32989039.

Quinet A, Tirman S, Jackson J, Šviković S, Lemaçon D, Carvajal-Maldonado C, González-Acosta D, Vessoni AT, Cybulla E, Wood M, Tavis S, Batista LFZ, Méndez J, Sale JE, Vindigni A. PrimPol-mediated adaptive response suppresses replication fork reversal in BRCA-deficient cells.
Mol. Cell 2020 Feb 6;77(3):461-474.e9. PMID: 31676232.

Fuh K, Mullen M, Blachut B, Stover E, Konstantinopoulos P, Liu J, Matulonis U, Khabele D, Mosammaparast N, Vindigni A. Homologous recombination deficiency real-time clinical assays, ready or not?
Gynecol. Oncol. 2020 Dec;159(3):877-886. PMID: 32967790.

Nayak S, Calvo JA, Cong K, Berthiaume E, Jackson J, Dash RC, Vindigni A, Hadden KM, Cantor S. Inhibition of the translesion synthesis polymerase, REV1 exploits replication gaps as a cancer vulnerability.
Science Advances 2020 10;6(24):eaaz7808. PMID: 32577513.

Mani C, Tripathi K, Luan S, Clark DW, Andrews JF, Vindigni A, Thomas G, Palle K. The multifunctional protein PACS-1 is required for HDAC2- and HDAC3-dependent chromatin maturation and genomic stability.
Oncogene. 2020 Mar;39(12):2583-2596. PMID: 31676232.

Meroni A, Vindigni A. ISG15 fast-tracks DNA replication.
J. Cell Biol. 2020 Aug 3;219(8):e202007028. PMID: 32687143.

Chen BR, Quinet A, Byrum AK, Jackson J, Berti M, Thangavel S, Bredemeyer AL, Hindi I, Mosammaparast N, Tyler JK, Vindigni A, Sleckman BP. XLF and H2AX Function in Series to Promote Replication Fork Stability.
J Cell Biol 2019 Jul 1;218(7):2113-2123 . PMID: 31123184.

Li S, Lavagnino Z, Lemacon D, Kong L, Ustione A, Ng X, Zhang Y, Wang Y, Zheng B, Piwnica-Worms H, Vindigni A, Piston DW, You Z. Ca(2+)-Stimulated AMPK-Dependent Phosphorylation of Exo1 Protects Stressed Replication Forks From Aberrant Resection.
Mol Cell 2019 Jun 20;74(6):1123-1137e6. PMID: 31053472.

Byrum AK, Carvajal-Maldonado D, Mudge MC, Valle-Garcia D, Majid MC, Patel R, Sowa ME, Gygi SP, Harper JW, Shi Y, Vindigni A, Mosammaparast N. Mitotic Regulators TPX2 and Aurora A Protect DNA Forks During Replication Stress by Counteracting 53BP1 Function.
J Cell Biol 2019 Feb 4;218(2):422-432. PMID: 30602538.

Byrum AK, Vindigni A*, Mosammaparast N*. Defining and modulating ‘BRCAness’.
Trends Cell Biol. 2019 Sep;29(9):740-751. *Co-corresponding authors. PMID: 31362850.

Carvajal-Maldonado D, Byrum AK, Jackson J, Wessel S, Lemacon D, Guitton-Sert L, Quinet A, Tirman S, Graziano S, Masson JY, Cortez D, Gonzalo S, Mosammaparast N, Vindigni A. Perturbing Cohesin Dynamics Drives MRE11 Nuclease-Dependent Replication Fork Slowing.
Nucleic Acids Res 2019 Feb 20;47(3):1294-1310. PMID: 29917110.

Last Updated: 11/12/2021 1:23:29 PM

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