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Mirit I. Aladjem, Ph.D.

Mirit I. Aladjem, Ph.D.

  • Center for Cancer Research
  • National Cancer Institute

RESEARCH SUMMARY

Dr. Aladjem studies cellular signaling pathways that regulate DNA synthesis. Since many regulatory pathways affecting chromosome duplication are deregulated in cancer, such studies can help understand cancer biology and elucidate the cellular response to chemotherapeutic drugs. Replication regulatory signals converge on replication origins, genomic regions that serve as replication starting points. Dr. Aladjem first reported that DNA sequence information can determine replication origin activity. Her team was the first to map replication origins on a whole genome scale, demonstrating a strong association between genome duplication and epigenetic modifications. Her current studies identify proteins that associate with replication origins to dictate if and when cells start or halt DNA synthesis. These studies will help decipher how normal and cancerous cells respond to signals that modulate genome duplication during chronological aging and after exposure to anti-cancer therapy.

Areas of Expertise

Publications

Selected Key Publications

The RepID-CRL4 ubiquitin ligase complex regulates metaphase to anaphase transition via BUB3 degradation.

Jang SM, Nathans JF, Fu H, Redon CE, Jenkins LM, Thakur BL, Pongor LS, Baris AM, Gross JM, OʹNeill MJ, Indig FE, Cappell SD, Aladjem MI.
Nat. Commun. 11(1): 24, 2020. [ Journal Article ]

The replication initiation determinant protein (RepID) modulates replication by recruiting CUL4 to chromatin.

Jang SM, Zhang Y, Utani K, Fu H, Redon CE, Marks AB, Smith OK, Redmond CJ, Baris AM, Tulchinsky DA, Aladjem MI.
Nat Commun.. 9(1): 2782, 2018. [ Journal Article ]

Dynamics of replication origin over-activation

Fu H, Redon CE, Thakur BL, Utani K, Sebastian R, Jang SM, Gross JM, Mosavarpour S, Marks AB, Zhuang SZ, Lazar SB, Rao M, Mencer ST, Baris AM, Pongor LS, Aladjem MI.
Nat Commun. 12(1): 3448, 2021. [ Journal Article ]

Convergence of SIRT1 and ATR Signaling to Modulate Replication Origin Dormancy

Thakur BL, Baris AM, Fu H, Redon CE, Pongor LS, Mosavarpour S, Gross JM, Jang SM, Sebastian R, Utani K, Jenkins LM, Indig FE, Aladjem MI.
Nucleic Acids Res. 50(9): 5111-5128, 2022. [ Journal Article ]

SLFN11 Blocks Stressed Replication Forks Independently of ATR.

Murai J, Tang SW, Leo E, Baechler SA, Redon CE, Zhang H, Al Abo M, Rajapakse VN, Nakamura E, Jenkins LMM, Aladjem MI, Pommier Y.
Mol Cell. 69(3): 371-84, 2018. [ Journal Article ]

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Team

Staff Scientist
Haiqing Fu, Ph.D.
Research Fellow
Robin Sebastian, Ph.D.
Postdoctoral Fellow (Visiting)
Anagh Ray, Ph.D.
Postdoctoral Fellow (Visiting)
Bhushan Thakur, Ph.D.
Postbaccalaureate CRTA
Nana Kusi

News

NIH Cell Cycle Interest Group Workshop

Wednesday, February 7, 2024, 10 am,

NIH Campus, Natcher building, Balconies A and B

 

Organized by: Munira Basrai, Mary Dasso and Mirit Aladjem

(Co-Chairs, NIH Cell Cycle Interest Group)

Agenda:

10:00 am: Keynote presentation:

Anja Katrin Bielinsky, PhD, University of Virginia School of Medicine

Rescue missions during mitosis: Alternative end-joining and mitotic DNA synthesis

11 am: 

Vinutha Balachandra, PhD, (Basrai Lab) NIH FARE Award winner

DNAJC9 prevents CENP-A mislocalization and chromosomal instability by maintaining H3-H4 supply

11:25 am:

Hindol Gupta, PhD, (Kelly Lab)  NIH FARE Award winner

The Spatial Arrangement of Centromeric Chromatin Templates Kinetochore Architecture"

11:50 am:

Chongji Chen, PhD, Earle Stadtman tenure-track investigator

Quantitative mapping of topoisomerase-modulated DNA supercoiling domains throughout the human genome