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The Kriwacki laboratory seeks to understand the molecular basis of regulation of cell division, apoptosis, and ribosome biogenesis, with special emphasis on the role of intrinsically disordered proteins (IDPs) in these vital biological processes. We apply structural biology and biophysical techniques (NMR spectroscopy, x-ray crystallography, calorimetry, AUC, SAXS/SANS, single-molecule fluorescence, etc.), as well as biochemical and cell biological methods, to study the details of biomolecular mechanisms from the test tube to cells.
We have a long-standing interest in understanding disorder-function relationships for two prototypical disordered proteins, p21 and p27, that are key regulators of the cyclin-dependent kinases (Cdks) that control cell division. We also use p27 as a model system for studies of small molecule/disordered protein interactions. Given the prevalence of disordered proteins in humans, and their frequent association with human diseases, the development of rational approaches to therapeutically modulate IDP function in cells could have a remarkable impact in improving human health.
Another area of interest is to understand the molecular mechanisms through which cytosolic p53 regulates the intrinsic mitochondrial pathway of apoptosis. In a series of studies, we discovered: 1) the molecular mechanisms through which Bcl-xL inhibits cytosolic p53; 2) how this inhibition is relieved by the pro-apoptotic BH3-only protein, PUMA; 3) how p53 directly activates the pro-apoptotic effector protein, BAX; and 4) how a disordered loop within Bcl-xL integrates post-translational modification signals to lower the threshold for BH3-only protein- and p53-dependent apoptosis.
We have a long-standing interest in understanding disorder-function relationships for two prototypical disordered proteins, p21 and p27, that are key regulators of the cyclin-dependent kinases (Cdks) that control cell division. We also use p27 as a model system for studies of small molecule/disordered protein interactions. Given the prevalence of disordered proteins in humans, and their frequent association with human diseases, the development of rational approaches to therapeutically modulate IDP function in cells could have a remarkable impact in improving human health.
Another area of interest is to understand the molecular mechanisms through which cytosolic p53 regulates the intrinsic mitochondrial pathway of apoptosis. In a series of studies, we discovered: 1) the molecular mechanisms through which Bcl-xL inhibits cytosolic p53; 2) how this inhibition is relieved by the pro-apoptotic BH3-only protein, PUMA; 3) how p53 directly activates the pro-apoptotic effector protein, BAX; and 4) how a disordered loop within Bcl-xL integrates post-translational modification signals to lower the threshold for BH3-only protein- and p53-dependent apoptosis.
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论文共 225 篇作者统计合作学者相似作者
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Yaqi Zhao,Nicholas J. Short,Hagop M. Kantarjian,Ti-Cheng Chang,Pankaj S. Ghate,Chunxu Qu,Walid Macaron,Nitin Jain,Beenu Thakral,Aaron H. Phillips,Joseph Khoury,Guillermo Garcia-Manero, Wenchao Zhang,Yiping Fan, Hui Yang,Rebecca S. Garris,Lewis F. Nasr,Richard W. Kriwacki,Kathryn G. Roberts,Marina Konopleva,Elias J. Jabbour,Charles G. Mullighan
Petri Polonen,Danika Di Giacomo,Anna Eames Seffernick,Abdelrahman Elsayed,Shunsuke Kimura, Francesca Benini,Lindsey E. Montefiori,Brent L. Wood,Jason Xu,Changya Chen,Zhongshan Cheng,Haley Newman,Jason Myers,Ilaria Iacobucci,Elizabeth Li,Jonathan Sussman,Dale Hedges, Yawei Hui, Caroline Diorio,Lahari Uppuluri,David Frank,Yiping Fan,Yunchao Chang,Soheil Meshinchi,Rhonda Ries, Rawan Shraim,Alexander Li,Kathrin M. Bernt,Meenakshi Devidas,Stuart S. Winter,Kimberly P. Dunsmore,Hiroto Inaba,William L. Carroll,Nilsa C. Ramirez,Aaron H. Phillips,Richard W. Kriwacki,Jun J. Yang,Tiffaney L. Vincent,Yaqi Zhao, Pankaj S. Ghate,Jian Wang,Colleen Reilly,Xin Zhou,Mathijs A. Sanders,Junko Takita,Motohiro Kato,Nao Takasugi,Bill H. Chang,Richard D. Press,Mignon Loh, Evadnie Rampersaud,Elizabeth Raetz,Stephen P. Hunger,Kai Tan,Ti-Cheng Chang,Gang Wu,Stanley B. Pounds,Charles G. Mullighan,David T. Teachey
NATURE (2024)
CURRENT OPINION IN STRUCTURAL BIOLOGY (2024)
Jun Zhan,Frank Harwood,Sara Ten Have,Angus Lamond,Aaron H. Phillips,Richard W. Kriwacki, Priyanka Halder, Monica Cardone,Gerard C. Grosveld
International Journal of Molecular Sciencesno. 18 (2024): 10042
bioRxiv the preprint server for biology (2024)
Amir Arabzade,Hazheen Shirnekhi,Srinidhi Varadharajan,Siri Ippagunta, Nicolas Laboe, David Gee, Devesh Bhimsaria,Erik Emanus,Alisha Kardian,Aaron Phillips, George Cambell, Cheong-Gil Park, Toler Freyaldenhoven,Bappaditya Chandra, Youlin Xia,Erik Bonten, Anushree Achari, Suresh Kandikonda,Alexandre Carisey,Benjamin Deneen,Kelsey Bertrand,Swarnendu Tripathi,Abbas Shirinifard, Becky Petersen, Sharon King,Daniel Stabley,Aaron Pitre,Richard Kriwacki,Stephen Mack
crossref(2024)
Bappaditya Chandra,Nicole L. Michmerhuizen,Hazheen K. Shirnekhi, Swarnendu Tripathi, Brittany J. Pioso, David W. Baggett,Diana M. Mitrea,Ilaria Iacobucci,Michael R. White,Jingjing Chen,Cheon-Gil Park,Huiyun Wu,Stanley Pounds,Anna Medyukhina,Khaled Khairy,Qingsong Gao,Chunxu Qu,Sherif Abdelhamed,Scott D. Gorman,Simranjot Bawa,Carolyn Maslanka, Swati Kinger,Priyanka Dogra,Mylene C. Ferrolino,Danika Di Giacomo,Cristina Mecucci,Jeffery M. Klco,Charles G. Mullighan,Richard W. Kriwacki
openalex(2023)
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作者统计
#Papers: 225
#Citation: 16372
H-Index: 63
G-Index: 127
Sociability: 7
Diversity: 3
Activity: 85
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