Agata Smogorzewska

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Agata Smogorzewska is a Polish-born scientist. She is an associate professor at Rockefeller University, heading the Laboratory of Genome Maintenance. [1] [2] Her work primarily focuses on DNA interstrand crosslink repair and the diseases resulting from deficiencies in this repair pathway, including Fanconi anemia and karyomegalic interstitial nephritis. [3] [4]

Contents

Early life and education

After finishing high school in Poland, [5] Smogorzewska completed her bachelor of science in molecular biology and biochemistry in 1995 at the University of Southern California. [3] She then went on to enroll in the tri-institutional M.D., Ph.D. program of Weill Cornell, Rockefeller and Sloan Kettering, finishing her Ph.D. thesis studies on the functions of the telomeric protein, TRF2, in the lab of Dr. Titia de Lange at Rockefeller University in 2002, and her medical degree from Weill Cornell in 2003. [3] [4] [5] Smogorzewska then went on to a residency in clinical pathology at the Massachusetts General Hospital from 2003–2006, becoming a postdoctoral researcher at Harvard Medical School between 2005–2009 under Dr. Stephen Elledge where she discovered the Fanconi anemia protein FANCI. [3] [4]

Career and research

Smogorzewska became an assistant professor at Rockefeller University in 2009 and was subsequently elevated to associate professor in 2015. [3] Her lab focuses on DNA repair mechanisms, particularly the interstrand crosslink repair pathway, which concerns the cellular mechanisms by which the two strands of DNA that have been covalently linked are excised, creating a double strand DNA break that is subsequently processed by factors in the Fanconi anemia and homologous recombination pathways. [3] [4] In particular, Smogorzewska is interested in identifying new genes that are involved in this repair process in order to reveal the mechanisms at play in human diseases that result from deficiencies in interstrand crosslink repair, including Fanconi anemia and karyomegalic interstitial nephritis. [3] [4] To this end, Smogorzewska has successfully identified SLX4, RAD51 and UBE2T as interstrand crosslink repair factors, as well as developed a mouse model of karyomegalic interstitial nephritis. [3] Recently, Smogorzewska has begun studies revolving around how replication stress is addressed by cells to promote genome stability. [4]

Smogorzewska is a part of the American Society for Biochemistry and Molecular Biology, [6] the New York Academy of Sciences, [7] the American Society of Clinical Investigation [8] and the American Society of Human Genetics [9]

Awards

[3] [5]

Selected publications

Regulation of telomerase by telomeric proteins – Annual Review of Biochemistry, 2004

Control of human telomere length by TRF1 and TRF2 – Molecular and Cellular Biology 2000

Identification of the FANCI protein, a monoubiquitinated FANCD2 paralog required for DNA repair – Cell, 2007

Different telomere damage signaling pathways in human and mouse cells – The EMBO Journal, 2002

Fanconi anaemia and the repair of Watson and Crick DNA crosslinks – Nature, 2013

DNA ligase IV-dependent NHEJ of deprotected mammalian telomeres in G1 and G2 – Current Biology, 2002

A genetic screen identifies FAN1, a Fanconi anemia-associated nuclease necessary for DNA interstrand crosslink repair – Molecular Cell 2010

Related Research Articles

<span class="mw-page-title-main">Fanconi anemia</span> Medical condition

Fanconi anaemia (FA) is a rare, AR, genetic disease resulting in impaired response to DNA damage in the FA/BRCA pathway. Although it is a very rare disorder, study of this and other bone marrow failure syndromes has improved scientific understanding of the mechanisms of normal bone marrow function and development of cancer. Among those affected, the majority develop cancer, most often acute myelogenous leukemia (AML), MDS, and liver tumors. 90% develop aplastic anemia by age 40. About 60–75% have congenital defects, commonly short stature, abnormalities of the skin, arms, head, eyes, kidneys, and ears, and developmental disabilities. Around 75% have some form of endocrine problem, with varying degrees of severity. 60% of FA is FANC-A, 16q24.3, which has later onset bone marrow failure.

<span class="mw-page-title-main">Telomeric repeat-binding factor 2</span> Protein

Telomeric repeat-binding factor 2 is a protein that is present at telomeres throughout the cell cycle. It is also known as TERF2, TRF2, and TRBF2, and is encoded in humans by the TERF2 gene. It is a component of the shelterin nucleoprotein complex and a second negative regulator of telomere length, playing a key role in the protective activity of telomeres. It was first reported in 1997 in the lab of Titia de Lange, where a DNA sequence similar, but not identical, to TERF1 was discovered, with respect to the Myb-domain. De Lange isolated the new Myb-containing protein sequence and called it TERF2.

<span class="mw-page-title-main">Telomeric repeat-binding factor 1</span> Protein-coding gene in humans

Telomeric repeat-binding factor 1 is a protein that in humans is encoded by the TERF1 gene.

<span class="mw-page-title-main">FANCD2</span> Protein-coding gene in the species Homo sapiens

Fanconi anemia group D2 protein is a protein that in humans is encoded by the FANCD2 gene. The Fanconi anemia complementation group (FANC) currently includes FANCA, FANCB, FANCC, FANCD1, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ, FANCL, FANCM, FANCN and FANCO.

<span class="mw-page-title-main">ERCC4</span> Protein-coding gene in the species Homo sapiens

ERCC4 is a protein designated as DNA repair endonuclease XPF that in humans is encoded by the ERCC4 gene. Together with ERCC1, ERCC4 forms the ERCC1-XPF enzyme complex that participates in DNA repair and DNA recombination.

<span class="mw-page-title-main">FANCF</span> Protein-coding gene in the species Homo sapiens

Fanconi anemia group F protein is a protein that in humans is encoded by the FANCF gene.

<span class="mw-page-title-main">FANCL</span> Protein-coding gene in the species Homo sapiens

E3 ubiquitin-protein ligase FANCL is an enzyme that in humans is encoded by the FANCL gene.

<span class="mw-page-title-main">FANCB</span> Protein-coding gene in the species Homo sapiens

Fanconi anemia group B protein is a protein that in humans is encoded by the FANCB gene.

<span class="mw-page-title-main">FANCI</span> Protein-coding gene in the species Homo sapiens

Fanconi anemia, complementation group I (FANCI) also known as KIAA1794, is a protein which in humans is encoded by the FANCI gene. Mutations in the FANCI gene are known to cause Fanconi anemia.

<span class="mw-page-title-main">DCLRE1B</span> Protein-coding gene in the species Homo sapiens

DNA cross-link repair 1B protein is a protein that in humans is encoded by the DCLRE1B gene.

<span class="mw-page-title-main">FANCM</span> Mammalian protein found in Homo sapiens

Fanconi anemia, complementation group M, also known as FANCM is a human gene. It is an emerging target in cancer therapy, in particular cancers with specific genetic deficiencies.

<span class="mw-page-title-main">SLX4</span> Protein involved in DNA repair

SLX4 is a protein involved in DNA repair, where it has important roles in the final steps of homologous recombination. Mutations in the gene are associated with the disease Fanconi anemia.

Telomere-binding proteins function to bind telomeric DNA in various species. In particular, telomere-binding protein refers to TTAGGG repeat binding factor-1 (TERF1) and TTAGGG repeat binding factor-2 (TERF2). Telomere sequences in humans are composed of TTAGGG sequences which provide protection and replication of chromosome ends to prevent degradation. Telomere-binding proteins can generate a T-loop to protect chromosome ends. TRFs are double-stranded proteins which are known to induce bending, looping, and pairing of DNA which aids in the formation of T-loops. They directly bind to TTAGGG repeat sequence in the DNA. There are also subtelomeric regions present for regulation. However, in humans, there are six subunits forming a complex known as shelterin.

Simon Joseph Boulton is a British scientist who has made important contributions to the understanding of DNA repair and the treatment of cancer resulting from DNA damage. He currently occupies the position of Senior Scientist and group leader of the DSB Repair Metabolism Laboratory at the Francis Crick Institute, London. He is also an honorary Professor at University College London.

Shelterin is a protein complex known to protect telomeres in many eukaryotes from DNA repair mechanisms, as well as to regulate telomerase activity. In mammals and other vertebrates, telomeric DNA consists of repeating double-stranded 5'-TTAGGG-3' (G-strand) sequences along with the 3'-AATCCC-5' (C-strand) complement, ending with a 50-400 nucleotide 3' (G-strand) overhang. Much of the final double-stranded portion of the telomere forms a T-loop (Telomere-loop) that is invaded by the 3' (G-strand) overhang to form a small D-loop (Displacement-loop).

<span class="mw-page-title-main">Titia de Lange</span> Dutch geneticist

Titia de Lange is the Director of the Anderson Center for Cancer Research, the Leon Hess professor and the head of Laboratory Cell Biology and Genetics at Rockefeller University.

<span class="mw-page-title-main">FAN1</span> Protein-coding gene in the species Homo sapiens

FANCD2/FANCI-associated nuclease 1 (KIAA1018) is an enzyme that in humans is encoded by the FAN1 gene. It is a structure dependent endonuclease. It is thought to play an important role in the Fanconi Anemia (FA) pathway.

<span class="mw-page-title-main">SLX4IP</span> Protein-coding gene in the species Homo sapiens

SLX4 interacting protein is a protein that in humans is encoded by the SLX4IP gene.

<span class="mw-page-title-main">Ketan J. Patel</span>

Ketan Jayakrishna Patel is a British-Kenyan scientist who is Director of the MRC Weatherall Institute of Molecular Medicine and the MRC Molecular Haematology Unit at the University of Oxford. Until 2020 he was a tenured principal investigator at the Medical Research Council (MRC) Laboratory of Molecular Biology (LMB).

<span class="mw-page-title-main">Orlando D. Schärer</span> Swiss chemist and biologist

Orlando David Schärer is a Swiss chemist and biologist researching DNA repair, genomic integrity, and cancer biology. Schärer has taught biology, chemistry and pharmacology at various university levels on three continents. He is a distinguished professor at the Ulsan National Institute of Science and Technology (UNIST) and the associate director of the IBS Center for Genomic Integrity located in Ulsan, South Korea. He leads the three interdisciplinary research teams in the Chemical & Cancer Biology Branch of the center and specifically heads the Cancer Therapeutics Mechanisms Section.

References

  1. ↑ "Agata Smogorzewska, M.D., Ph.D. Appointed to JBC Editorial Board | Tri-Institutional MD-PhD Program". mdphd.weill.cornell.edu. Retrieved 2019-10-03.
  2. ↑ "Mice engineered with rare kidney disease shed light on how cells repair broken DNA". ScienceDaily. Retrieved 2019-10-03.
  3. 1 2 3 4 5 6 7 8 9 "Agata Smogorzewska". Our Scientists. Retrieved 2019-09-07.
  4. 1 2 3 4 5 6 "Smogorzewska Laboratory". Smogorzewska Laboratory. Retrieved 2019-09-07.
  5. 1 2 3 "Agata Smogorzewska, MD, PhD". Pershing Square Foundation. Retrieved 2019-09-07.
  6. ↑ "News | Member Update". www.asbmb.org. Retrieved 2019-09-07.
  7. ↑ "Genome Integrity Discussion Group February 2017". New York Academy of Sciences. Archived from the original on 2020-09-28.
  8. ↑ "JCI Editor's update: Plan S, JCI Scholars, recent reviews, and more". The American Society for Clinical Investigation. Archived from the original on 2020-08-08.
  9. ↑ "Poster Listing | ASHG 2012 Annual Meeting". www.ashg.org. Retrieved 2019-09-07.
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