BiographyCurrently Dr. Nasim is a Senior Lecturer in Therapeutics at the School of Pharmacy and Medical Sciences, the University of Bradford, UK. He is an Executive Member, Research and Knowledge Transfer Committee, Faculty of Life Sciences, University of Bradford, Local Ambassador, the Biochemical Society, United Kingdom, Adviser, the Commonwealth Scholarship Commission, United Kingdom, Executive Member, Global Network of Bangladeshi Biotechnologists (GNOBB). He has been the member of Editorial Boards of a number of international journals including Journal of Bioscience, International Journal of Perception in Public Health and acted as a Guest Editor for the journal Pain Research and Management.
His research interests focus in the broader areas of Translational Medicine (gene identification to drug discovery). He has identified a few key genes that cause disorders such as Pulmonary Hypertension and blood cancer and identified novel diagnostics and therapeutics. Importantly, his discoveries are being taught at the university level and he is the inventor of a number of diagnostic and therapeutic patents.
His contributions to science include publications in scientific journals, articles to local and national Bangladeshi daily newspapers and intellectual supports to scientific community around the world. He has published 70 articles including research papers in journals like Nature Genetics, Nature Protocols, Nature Communications, Nucleic Acids Research, Human Molecular Genetics. His research has been extensively highlighted in news media across the globe as evidenced in his interviews with CBA News (USA), Labmate https://www.labmate-online.com/news/news-and-views/5/university-of-bradford/diagnostic-clues-found-for-pah/48687 (UK) and Daily Prothom-alo (Bangladesh). He writes regularly in newspapers including the daily Jugantor, Daily Prothom-alo and Lalmonirhat Barta and edited books inaugurated by the Prime Minister of the Peoples Republic of Bangladesh.
He has been promoting science in Bangladesh. He is the founder and Chief Adviser of the organization called Centre for Health Agriculture and Socio-economic Advancements (CHASA), which was incepted in 2008 at Lalmonirhat, Bangladesh. Since its inception, CHASA has provided more than 150 scholarships to local students at various levels from primary to college and supported research projects at universities which resulted in a few scientific publications.
Dr. Nasim received his Ph.D degree from the University of Manchester Institute of Science and Technology (UMIST), UK. In his student life, he received 18 scholarships from various countries including Bangladesh, Switzerland, USA and UK. In fact, he is the first ever Bangladeshi student who received the Swiss Govt. Scholarship.
Dr. Nasim was a co-recipient of the Best Scientist Award 2008 of Lalmonirhat Municipality (Bangladesh) and received nomination for the ‘Best Non-resident Bangladeshi Scientist-2019’ of Global Network of Bangladeshi Biotechnologists (GNOBB).
ResearchInvestigation of BMP and TGFb signalling events to resolve pulmonary arterial hypertension (PAH)
PAH is a devastating cardiovascular disorder caused by narrowing of blood vessels in the lungs and in the absence of therapy leads to right heart failure and death. We have established that nonsense mutations in the BMPR2 gene underlie the majority of the inherited forms of the disease. BMPR2 mutations contribute to stoichiometric imbalance in the receptor complex leading to dysfunctional signalling (Nasim et al., 2008, 2012). Mutations are also found in the SMAD family genes but they represent an infrequent cause of the disease (Nasim et al., 2011). Mutations in the BMPR2 gene potentiate TGFb signalling (Nasim et al., 2012) and prostacyclins, the commonly used therapy for severe PAH inhibit this pathway (Ogo et al., 2013). Taken together these observations suggest that agents that inhibit the overactive TGFb signalling and/or promote the BMP signalling may provide protection in PAH. We identified some small molecule agents that restore the balance between the TGFb and BMP pathways and rescued abnormal proliferation and apoptosis in cell-based models of PAH (Siddiqui et al., 2013). Structure guided virtual screening identified additional compounds which elicited anti-TGFb activity in cell-based assays. A number of ‘leads’ have been identified through a medicinal chemistry programme (unpublished data). The major objectives of this part of research are to investigate (a) the molecular mechanisms by which the TGFb signalling is activated in PAH, and (b) therapeutic resolution of PAH by chemical agents that restore the balance between BMP and TGFb signalling pathways.
M.T. Nasim, T. Ogo, H.M. Chowdhury and R.C. Trembath. Human Mol Genetics (doi 10.1093/hmg/DDS073), 2012
M T. Nasim, T. Ogo, M. Ahmed, R. Randall, et al. Human Mutation 12:1385-89, 2011
M.T. Nasim, A.G. Ghouri, B.P. Patel, et al., Hum Mol Genet (11):1683-94, 2008
M. T. Nasim, S. Jaenecke, A. Belduz, et al., J. Biol. Chem. 275: 14646-14852, 2000
T. Ogo, H.M. Chowdhury, N.W. Morrell, R.C. Trembath and M.T. Nasim. (American Journal of Respiratory Cell and Molecular Biology), 2013.
H. M. Chowdhury, M. A. Sidiqui, S. Kanneganti, N. Sharmin and M. T. Nasim*. Hum Mol Genet. 27: 373-384, 2018
H. M. Chowdhury, N. Sharmin, M. Baran, L. Long, N.W. Morrell, R. C. Trembath and M. T. Nasim*.Hum Mol Genet Feb 2019
M.A Siddiqui, M. Ahmed, T. Ogo, M. Hossain, H.M. Chowdhury, L.Long, F. Khan, N. W. Morrell, R.C. Trembath and M.T. Nasim (unpublished).
Therapeutic resolution of nonsense-associated genetic disorders by promotion of translation readthrough
There are more than 3000 genetic disorders including cystic fibrosis, muscular dystrophy and PAH caused by nonsense mutations. Agents that promote translation readthorugh may provide therapeutic intervention. We have established cell based assay system which is capable of screening drugs that promote translational readthorugh (Nasim et al., 2000, 2005, 2008 and patent applications). Using these techniques, hits have been identified through screening of a small molecule library, which are now being tested whether they rescue BMPR2-mediated cellular defects in PAH. The major objectives of this part of research are to (a) identify agents that promote readthrough and (b) test whether promotion of readthrough by small molecule agents can provide protection in PAH and in other nonsense associated genetic disorders.
M.T. Nasim, A.G. Ghouri, B.P. Hum Mol Genet (11):1683-94, 2008.2.
M.T. Nasim* and R.C. Trembath. Nucleic Acids Res. 33(7): e66 (8 pages), 2005.
M. T. Nasim, S. Jaenecke, A. Belduz, H. Kollmus, L. Flohe and J.E.G. McCarthy; J. Biol. Chem. 275: 14646-14852, 2000.
Modulation of Splicing in human diseases Identification of non-canonical factors regulating tissue-specific alternative splicing
Mutations in pre-mRNA splicing signals account for both inherited and acquired defects, are now increasingly recognized as causes of human diseases. Improvements of our current understanding of alternative splicing regulation may therefore provide opportunities to counter the consequences of mutation. Although many components of the spliceosomal complex have been identified, their roles in splicing regulation (e.g. activator or inhibitor) are not fully understood. We and others have reported the involvement of non-canonical proteins and micro-RNAs (miRNAs) in regulating splicing events, which suggest that this process is controlled by many more factors than previously thought. Hence, constructing a genome-wide map is essential in revealing the mechanisms involved. Identification of such factors and the characterization of ‘ex-vivo’ networks require a system capable of screening a large number of samples. The absence of a generic approach prompted me to develop rapid assay systems based on enzymatic and fluorescence activities (Nasim et al., 2002, 2006, 2008, 2011). Each method comprises two distinct signals either fluorescence or luminescence which can be monitored in mammalian cells, providing a basis for high throughput format. In this project, we seek to construct a genome-wide map for splicing regulation employing these established approaches and identify novel non-canonical factors including proteins, chemicals and miRNAs that modulate tissue-specific alternative splicing of the human tropomyosin 3 (TPM3) gene. This study will be of substantial use to the study of alternative and aberrant splicing of a wide range of disorders, will greatly enhance the identification of novel drug targets and therapies as well as the development of novel diagnostic tests.
Therapeutic resolution of myodysplastic syndrome (MDS) by modulation of aberrant splicing Myelodysplastic syndromes (MDS) are the most common adult myeloloid malignancy in the UK and approximately 30% of patients will transform to secondary acute myeloid leukaemia (AML), which has a poor prognosis. There is no cure for MDS and current maintenance therapies were all established prior to the realisation that MDS have substantial genetic components. Hence, there is a need to develop a novel therapy which accounts for the biochemical consequences of such gene defects. We have previously demonstrated that heterozygous missense mutations in U2AF1 (encoding U2AF35, the 35 kDa component of the heterodimeric U2 auxiliary factor), underlie the majority of MDS. We have demonstrated that these mutations potentiate overactive splicing and alter downstream gene isoform expression and therefore contribute to abnormal haematopoiesis. Our preliminary data indicate that agents that inhibit this overactive splicing may provide beneficial effects in vitro and in vivo mouse models. The major aim of this project is to develop a targeted chemotherapy for MDS by inhibition of overactive splicing activity of pathogenic nonsense alleles using small molecule agents. In this project we seek to utilise and expand on our preliminary observations to identify small molecule agents capable of targeting U2AF1-mediated splicing defects for selective therapy. Compounds will be identified by means of cell-based and in silico screening and validation will be performed in K562 myeloid cell line models and bone marrow cells derived from MDS patients.
M. T. Nasim, H. M. Chowdhury and I. C. Eperon. Nucleic Acids Res. 30: e109, 2002.
M.T. Nasim and R.C. Trembath. Nucleic Acids Res. 33(7): e66 (8 pages), 2005.
M.T. Nasim and I. C. Eperon. Nature Protocols 1(2):1022-1028, 2006.
M. T. Nasim, T. K. Chernova, H.M. Chowdhury, B. Yue and I. C. Eperon. Hum Mol Genet. 12:1337-1348, 2003.
Suraweera A, Lim Y, Woods R, Birrell GW, Nasim T, Becherel OJ, Lavin MF. Hum Mol Genet.(18):3384-96, 2009.
Katiyar S, Maria A, Covarrubias Y, Casimiro M.C, Zhou J, Jaio X, Hyslop T, Nasim T, Fortina P, Pestell R. Cancer Research; 72(4):1023-34), 2012.
T. Graubert, D Shen, T. Nasim, D. Link, M. Tomasson, P. Westervelt, J. DiPersio, E. Mardis, T. Ley, R. Wilson, and M. Walter. Nature Genetics 44(1):53-7, 2012.
M. Brioschi, S. Lento, S. Barcella, M.T. Nasim, S. Ghilardi, S. Barbieri, E. Tremoli and C. Banfi. Data Brief. ; 25;3:117-9, 2015 § S. Lento, M. Brioschi, S. Barcella,
M.T. Nasim, S. Ghilardi, S. Barbieri, E. Tremoli and C. Banfi. J Proteomics.;119:75-89, 2015
Breast cancer gene function study of Bangladeshi population
Breast cancer (BC) is the leading cause of cancer deaths among women worldwide, with an estimated 1.7 million cases and > 0.5 million deaths per year. BC is the most common cancer in Bangladeshi women and is predicted to be an increasingly important cause of morbidity and mortality in the next 20 years. To date, no population-based cancer registries or a central registry with comprehensive national cancer data is available. For Bangladeshi women with human epidermal growth factor receptor (HER2), estrogen receptor (ER) and progesterone receptor (PR) negative patients (~25%) have no effective targeted therapies. In addition, it is currently not known whether these patients carry mutations in either BRCA1 or BRCA2 genes as there is no genetic screening system available in Bangladesh. Mutations in other genes such as TP53, PTEN and CASP8 are also found in BC patients worldwide but their penetrance in Bangladeshi populations remains unknown. The major objective of this research is to determine the genetic landscape of Bangladeshi BC patients to inform better diagnosis, prognosis, treatment and counselling.
Dr. Klaus Pors, Institute of Cancer Therapeutics (University of Bradford)
Dr. Steve Shnyder, Institute of Cancer Therapeutics (University of Bradford
Prof. Paul Loadman, Institute of Cancer Therapeutics (University of Bradford)
Prof. Tim Palmer, School of Pharmacy (University of Bradford)
Prof. Colin Wright, School of Pharmacy (University of Bradford)
Prof. Richard Trembath (Queen Marry London, UK)
Prof. N.W. Morrell (Cambridge, UK)
Prof. Ian Eperon (Leicester, UK)
Prof. Lan Zhao and Prof. Martin Wilkins (Imperial College, UK)
Prof.. Matt Walter (Washington University, USA)
Dr. Yi-Tao, (Rochester University, USA)
Dr. Christina Bunfii, (IRCCS, Milano, Italy)
Dr. Hao Jiang, (University of Alabama at Birmingham, USA)
|Name||Prof. Nicholas Morrell|
|Company||University of Cambridge|
|Name||Prof. Richard Trembath|
|Company||King's College London|
|Name||Prof. Ian Eperon|
|Company||University of Leicester|
|Name||Dr. Hao Jiang|
|Company||University of Alabama at Birmingham|
|Name||Dr. Christina Bunfii|
|Name||Prof. Matt Walter|
|Role||Masters (Research) Student|
|Project||Functional consequences of BMPR2 mutations in pulmonary arterial hypertension|
|Role||Masters (Research) Student|
|Project||Identification of Novel Factors that Regulate Tissue Specific Alternative Splicing|
|Project||Resolution of pulmonary arterial hypertension by novel small molecule agents|
|Project||Resolution of PAH by natural products|
|Project||Resolution of pulmonary arterial hypertension (PAH) by modulating BMP and TGFb signalling pathways|
|Project||Prostanoid-mediated inhibition of IL-6 trans-signalling in pulmonary arterial hypertension; a role for Epac1-mediated induction of "suppressor of cytokine signalling 3" (SOCS3)|
|Name||Dr. Khaled Habas|
|Role||Senior Postdoctoral Researcher|
|Project||Development of diagnostic biomarker for pulmonary arterial hypertension (PAH)|
|Name||Dr. Merve Baran|
|Project||Determination of the efficacy of natural products in pulmonary artrial hjypertension|
- 01-JAN-00: University of Manchester - PhD
- 01-JAN-13: King’s College London - Visiting Senior Research Fellow
- 01-JAN-08: Agriculture and Socio-economic Advancements (CHASA), Bangladesh - Founder and Chief Adviser (Honorary)
- 01-JAN-08: King’s College London - Senior Research Fellow
- 01-JAN-06: King’s College London - Research Associate
- 01-JAN-06: University of Leicester - Research Associate
- 01-JAN-00: University of Leicester - Research Associate
- 01-JAN-94: University of Geneva - Post-graduate Research Fellow
- , Member: American Thoracic Society
- , Member: Biochemical Society (UK)
- Research and Knowledge Transfer, Faculty of Life Sciences,
- 01-JAN-08: - Best Scientist Award
- 01-JAN-19: - Outstanding Non-Resident Bangladeshi Scientists (Nomination)
- Academic Advisor: Academic Adviser: Commonwealth Scholarship Commission
- Executive Member: Executive Member: Global Network of Bangladeshi Biotechnologists (GNOBB)
- Life Member: Life Member: Global Network of Bangladeshi Biotechnologists (GNOBB)
- Local Ambassador: The Biochemical Society, UK
- Executive Member: Journal of Bioscience
|Peer Reviewed Journal|
|Title||BMPRII deficiency impairs apoptosis via the BMPRII-ALK1-BclX-mediated pathway in pulmonary arterial hypertension (2019)|
|Authors||Chowdhury H.;Sharmin N.;Yuzbasioglu Baran M.;Long L.;Morrell N.;Trembath R.;Nasim M.|
|Journal||Human Molecular Genetics|
|Title||BMPRII deficiency impairs apoptosis via the BMPRII-ALK1-BclX-mediated pathway in pulmonary arterial hypertension (PAH) (2019)|
|Authors||Chowdhury, H.M.; Sharmin, N.; Yuzbasioglu Baran, M.; Long, L.; Morrell, N.W.; Trembath, R.C.; Nasim, Md. Talat|
|Title||Aminoglycoside-mediated promotion of translation readthrough occurs through a non-stochastic mechanism that competes with translation termination (2018)|
|Authors||Chowdhury H.;Siddiqui M.;Kanneganti S.;Sharmin N.;Chowdhury M.;Nasim M.|
|Journal||Human Molecular Genetics|
|Title||Aminoglycoside-mediated promotion of translation readthrough occurs through a non-stochastic mechanism that competes with translation termination (2017)|
|Authors||Chowdhury, H.M.; Siddiqui, M.A.; Kanneganti, S.; Sharmin, N.; Chowdhury, M.W.; Nasim, Md. Talat|
|Title||AKAP95 regulates splicing through scaffolding RNAs and RNA processing factors (2016)|
|Authors||Hu, J.; Khodadadi-Jamayran, A.; Mao, M.; Shah, K.; Yang, Z.; Nasim, Md. Talat; Wang, Z.; Jiang, H.|
|Title||Proteomics of tissue factor silencing in cardiomyocytic cells reveals a new role for this coagulation factor in splicing machinery control (2015)|
|Authors||Lento, S.; Brioschi, M.; Barcella, S.; Nasim, Md. Talat; Ghilardi, S.; Barbieri, S.S.; Tremoli, E.; Banfi, C.|
|Title||Data for proteomic analysis of murine cardiomyocytic HL1 cells treated with siRNA against tissue factor (2015)|
|Authors||Brioschi, M.; Lento, S.; Barcella, S.; Nasim, Md. Talat; Tremoli, E.; Banfi, C.|
|Title||Inhibition of Overactive Transforming Growth Factor–β Signaling by Prostacyclin Analogs in Pulmonary Arterial Hypertension (2013)|
|Authors||Ogo, T.; Chowdhury, H.M.; Yang, J.; Long, T.; Li, X.; Torres Cleuven, Y.N.; Morrell, N.W.; Schermuly, R.T.; Trembath, R.C.; Nasim, Md. Talat|
|Title||Pulmonary arterial hypertension: molecular genetic basis and emerging treatments (2012)|
|Authors||Siddiqui, M.A.; Ogo, T.; Nasim, Md. Talat|
|Title||BMPR-II deficiency elicits pro-proliferative and anti-apoptotic responses through the activation of TGFbeta-TAK1-MAPK pathways in PAH (2012)|
|Authors||Nasim, Md. Talat; Ogo, T.; Chowdhury, H.M.; Zhao, L.; Chen, C-n.; Rhodes, C.; Trembath, R.C.|
|Title||Recurrent mutations in the U2AF1 splicing factor in myelodysplastic syndromes (2012)|
|Authors||Graubert, T.A.; Shen, D.; Ding, L.; Okeyo-Owuor, T.; Lunn, C.L.; Shao, J.; Krysiak, K.; Harris, C.C.; Koboldt, D.C.; Larson, D.E.; McLellan, M.D.; Dooling, D.J.; Abbott, R.M.; Fulton, R.S.; Schmidt, H.; Kalicki-Veizer, J.; O'Laughlin, M.; Grillot, M.; Baty, J.; Heath, S.; Frater, J.L.; Nasim, Md. Talat; Link, D.C.; Tomasson, M.H.; Westervelt, P.; DiPersio, J.F.; Mardis, E.R.; Ley, T.J.; Wilson, R.K.; Walter, M.J.|
|Title||Molecular genetic characterization of SMAD signaling molecules in pulmonary arterial hypertension (2011)|
|Authors||Nasim, Md. Talat; Ogo, T.; Ahmed, Mohammed I.; Randall, R.; Chowdhury, H.M.; Snape, K.M.; Bradshaw, T.Y.; Southgate, L.; Lee, G.J.; Jackson, I.; Lord, G.M.; Gibbs, J.S.; Wilkins, M.R.; Ohta-Ogo, K.; Nakamura, K.; Girerd, B.; Coulet, F.; Soubrier, F.; Humbert, M.; Morrell, N.W.; Trembath, R.C.; Machado, R.D.|
|Title||Stoichiometric imbalance in the receptor complex contributes to dysfunctional BMPR-II mediated signalling in pulmonary arterial hypertension (2008)|
|Authors||Nasim, Md. Talat; Ghouri, A.; Patel, B.; James, V.; Rudarakanchana, N.; Morrell, N.W.; Trembath, R.C.|