Department of Chemistry

Search

FourSquare

Kabirul Islam

Assistant Professor

Contact

1307 Chevron Science Center
Chevron Science Center
219 Parkman Avenue

Pittsburgh, PA 15260
412-624-5061

Research Overview

Chemical Approaches towards Diagramming Epigenetic Network in Human Development and Disease

Organic Synthesis, Bioorganic Chemistry, Small Molecule Therapeutics, Biochemistry, Protein Engineering and ‘Chromatinomics’ (Chromatin-based Proteomics and Genomics)

We are actively engaged in investigating molecular details of biological processes, particularly those where small organic functionalities when coupled to macromolecules dictate the course of living systems. Chemical modifications on genetic material (DNA) and its packaging elements (Histones) coupled with ATP-dependent chromatin remodeling constitute an epigenetic mechanism that is known to regulate gene transcription, cellular differentiation and organismal development. However, molecular understanding of how these chemical events (establishment and reversal of methylation, acetylation; and ATP hydrolysis) occurring in chromatin landscape control nuclear processes is just beginning to emerge. The focus of our research is to apply chemical principles and methods in understanding these processes that are hard to define by conventional biological methods alone. Given the highly dynamic nature of chromatin-templated events to allow fast cellular responses to developmental/external cues, the scope for applying small-molecule tools to deconvolute the complexity of these signaling pathways is enormous. We are focusing on three areas of epigenetic mechanisms that are at best partially understood: (i) reversal of DNA methylation, (ii) recognition of chromatin modification by ‘reader’ modules, and (iii) ATP-dependent chromatin remodeling.

Deregulation in above-mentioned processes can cause chromosomal instability, and eventually lead to multiple disorders including cancer and neurological diseases. Molecular rationale linking these epigenetic events to disease states is lacking. For example, how  mutations in various gene products in these pathways play role in tumorigenesis, tumor progression and metastasis is not completely clear. We envision an active research program to potentiate therapeutic endeavors through the following interconnected  goals: (i) to develop novel chemical tools to probe epigenetic processes both in normal and disease states, (ii) to identify new epigenetic drug targets, and (iii) to develop small molecule modulators for these targets.

Our research takes a multidisciplinary approach that integrates organic synthesis, protein engineering, mechanistic biochemistry, proteomics and transcriptomics in order to interrogate cellular machineries towards molecular understanding of epigenetic mechanisms in human health and disease.

Awards

  • Visiting Research Fellowship by Starr Cancer Consortium (2010)
  • Graduate Research Fellowship by Council for Scientific and Industrial Research, New Delhi, India (1999-04)
  • Institute Proficiency Prize, Department of Chemistry, Indian Institute of Technology, Kharagpur, India (1999)
  • Institute Silver Medal, Indian Institute of Technology, Kharagpur, India (1999)
  • Summer Research Fellowship, Tata Institute of Fundamental Research, Mumbai, India (1998)

Publications

“Using Azido Analogue of S-Adenosyl-L-methionine for Bioorthogonal Profiling of Protein Methylation,” Blum, G.; Islam, K.; Luo, M., Curr. Protoc. Chem. Biol., Vol. 5, 2013, Pages 45
“Profiling chromatin methylation with engineered posttranslation apparatus within living cells.,” Wang, R.¶; Islam, K.¶; Zheng, W.; Liu, Y.; Tang, H.; Blum, Gil.; Deng, H.; Luo, L., J. Am. Chem. Soc., Vol. 135, 2013, Pages 1048
“Se-adenosyl-L-selenomethionine cofactor analogue as a reporter of protein methylation.,” Bothwell, I.; Islam, K.; Cheng, Y.; Zheng, W..; Blum, G.; Deng, H.; Luo, M., J. Am. Chem. Soc., Vol. 134, 2012, Pages 14905
“Bioorthogonal profiling of protein methylation using azido derivative of S-adenosyl-L-methionine.,” Islam, K.; Bothwell, I.; Cheng, Y.; Sengelaub, C.; Wang, R.; Deng, H.; Luo, M., J. Am. Chem. Soc., Vol. 134, 2012, Pages 5909
“Expanding cofactor repertoire of protein lysine methyltransferase for substrate labeling.,” Islam, K.; Zheng, W.; Yu, H.; Deng, H.; Luo, M., ACS Chem. Biol., Vol. 6, 2011, Pages 679
“Myosin V inhibitor based on ‘privileged’ chemical scaffolds.,” Islam, K.; Olivares, A. O.; De La Cruz, E. M.; Kapoor, T. M., Angew. Chem. Int. Ed. Eng., Vol. 49, 2010, Pages 8484
“In situ cryo-crystallization of diphenyl ether: C-H…π mediated polymorphic forms.,” Choudhury, A. R.; Islam, K.; Krichner, M. T; Mehta, G.; Guru Row, T. N., J. Am. Chem. Soc., Vol. 126, 2004, Pages 12274
“Enantioselective total synthesis of (-)-Epoxyquinols A and B. Novel, convenient access to chiral epoxyquinone building blocks through enzymatic desymmetrization.,” Mehta, G.; Islam, K., Tetrahedron Lett., Vol. 45, 2004, Pages 3611
“Total synthesis of the novel NF-κB inhibitor (-)-Cycloepoxydon.,” Mehta, G.; Islam, K., Org. Lett., Vol. 6, 2004, Pages 807
“Enantioselective total syntheses of (+) and (-)-ottelione A and (+) and (-)-ottelione B. Absolute configuration of the novel, biologically active natural products.,” Mehta, G.; Islam, K., Tetrahedron Lett., Vol. 44, 2003, Pages 6733
“Total synthesis of novel angiogenesis inhibitors epoxyquinols A and B.,” Mehta, G.; Islam, K., Tetrahedron Lett., Vol. 44, 2003, Pages 3569
“Total Synthesis of epi-Otteliones.,” Mehta, G.; Islam, K., Org. Lett., Vol. 4, 2002, Pages 2881
“Defining efficient enzyme-cofactor pairs for bioorthogonal profiling of protein methylation,” Islam K, Chen Y, Wu H, Bothwell IR, Blum GJ, Zeng H, Dong A, Zheng W, Min J, Deng H, Luo M., Proc Natl Acad Sci U S A., Vol. 110, 2013, Pages 16778-83