Lilian Kabeche, PhD
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About
Titles
Assistant Professor
Biography
Lilian Kabeche, Ph.D., joined the Yale faculty in 2019 as an Assistant Professor in Molecular Biophysics and Biochemistry and a member of the Cancer Biology Institute. Dr. Kabeche attended the University of Miami, where she majored in Microbiology and Immunology (B.S. 2007). She did her Ph.D. in Biochemistry at Dartmouth College in Dr. Duane Compton’s lab, where she studied how healthy cells ensure that chromosomes are correctly segregated during cell division (mitosis). She went on to do her post-doctoral work in Dr. Lee Zou’s lab at Mass General Hospital, Harvard University, where she identified a novel role for the DNA damage repair kinase, ATR, in mitosis. Her lab's current work uses single-cell techniques to define how the DNA damage pathway pathway promotes genome stability throughout the cell cycle.
Thus far, her lab has elucidated that members of the DNA damage response pathway function in mitosis to ensure that chromosomes are correctly segregated, interact with the immune system, and promote cell-autonomous and non-autonomous mechanisms to eliminate damaged cytosolic DNA and regulate genome integrity through epigenetic regulation of the centromere. These works shift the current paradigm that components of the DNA damage response pathway have a singular function- to recognize and repair DNA. Dr. Kabeche aims to leverage her lab's discoveries to devise better therapeutic strategies for cancer treatment using DNA damage response kinase inhibitors.
Appointments
Molecular Biophysics and Biochemistry
Assistant ProfessorPrimary
Other Departments & Organizations
- Biochemistry, Quantitative Biology, Biophysics and Structural Biology (BQBS)
- Center for RNA Science and Medicine
- Molecular Biophysics and Biochemistry
- Molecular Cell Biology, Genetics and Development
- Radiobiology and Genome Integrity
- Yale Cancer Center
- Yale Combined Program in the Biological and Biomedical Sciences (BBS)
- YCC Diversity, Equity, and Inclusion
Education & Training
- PhD
- Dartmouth College, Biochemistry
- BS
- University of Miami, Microbiology and Immunology
Research
Overview
The Kabeche lab strives to understand the interplay between chromosomal instability (CIN) and DNA damage response (DDR) defects in cancers and develop new strategies to target CIN in cancer therapy. Chromosomal instability (CIN) is hallmark of cancer whereby cells continuously gain and/or lose whole chromosomes. CIN is present in over 90% of solid tumors and 50% hematopoietic cancers and is correlated with immune evasion, drug resistance, and increased metastasis and poor patient prognosis. CIN itself is self-propagating and can lead to increased genomic instability, whereby chromosome missegregation events can lead to DNA damage during interphase. DNA damage in turn can cause chromosome missegregation creating further genomic instability upon missegregation events. Therefore, it is necessary to understand how the DDR pathway and the mitotic machinery work together and independently to promote genome stability. We have two major areas of research:
Area 1: Investigating the role of the DNA damage repair pathway in mitosis.
A major focus in the lab is investigating how components of the DNA damage response pathway work in mitosis outside of their canonical functions of repairing DNA. We have focused much of our time investigating the role of Ataxia telangiectasia and Rad3 related (ATR) kinase, a master regulator of the DDR pathway. Our previous work demonstrated that ATR is an important component of the centromere and mitotic machinery that ensures faithful chromosome segregation. Our previous work demonstrated that during mitosis, ATR acts independent of its function as part of the DNA damage response pathway and helps promote the activity of a major mitotic kinase: Aurora B. We continue to further study how ATR is activated, regulated and fully elucidate the mechanism by which ATR regulates mitotic processes to ensure that cells segregate their chromosomes faithfully.
In addition to studying ATR, we have also made exciting discoveries on novel functions of other components of the DDR pathway in mitosis.
Area 2: Investigating non-canonical roles of DNA damage repair proteins in interphase.
A second major focus in the lab is investigating how components of the DNA damage response pathway work outside of their function as part of the DNA damage response pathway to promote genome stability. Through our studies we discovered that ATR promotes genome stability by maintaining centromere identity through its regulation of histone chaperones, including DAXX. Loss of ATR, even in the absence of DNA damage led to an inappropriate deposition of H3.3 histones and loss of CENP-A histones at centromeres, leading a loss of centromere identity. This work has opened up many questions of the mechanism by which ATR regulates DAXX and other histone chaperones and how ATR is regulated in the absence of DNA damage. We aim to study this to further understand how healthy and cancer cells are affected by ATR inhibitors, which are currently being tested in the clinic.
Links & Media
News
- May 17, 2023Source: Yale West Campus
Multi-tasking protein has potential to protect against disease
- May 19, 2021Source: Yale West Campus
Two Yale Scientists Receive the Pershing Square Sohn Prize for Young Investigators in Cancer Research
- May 18, 2021
Two Yale Cancer Center scientists awarded the Pershing Square Sohn Prize for Young Investigators in Cancer Research