Special seminar invitation

[Office Biotechnology]

Dear all,

You are cordially invited for a Special Seminar as per details given below:

Speaker:

Dr Dharmaraja T Allimuthu

Post-doctoral Research Associate, 

School of Medicine, Dept. of Genetics and Genome Sciences and Comprehensive Cancer Centre, 

Case Western Reserve University School of Medicine, Cleveland, OH 44106

Title of the talk:

Chemical biology-based approaches for small molecule therapeutic discovery and extending into covalent chemical probes

Date and Time  :  28th August 2018 at 11 am

Venue:  Biotechnology seminar hall

Bio of the Speaker:

Education:

PhD: 2010-2015, Chemical biology, Indian Institute of Science Education and Research Pune, India 

(Mentor: Prof. Harinath Chakrapani; Thesis Title: Synthesis and evaluation of small molecule based reactive oxygen species (ROS) generators as therapeutics) 

MSc: 2003-2005, Chemistry, 7.01/10.00 CGPA, First Class. School of Chemistry, Bharathidasan University, Trichy, India. 

BSc: 2000-2003, Chemistry, 70.2%, First Class. Department of Chemistry, Periyar University, Salem, India.

Honors and Awards

1.Aug-2018: Got selected as a Director’s Postdoctoral Fellow in Los Alamos National Laboratory

2.Mar-2013: Outstanding Presentation of a Research Poster Award in “2nd UK – India Royal Society of Chemistry -Medchem Congress” at Indian Institute of Chemical Technology, Hyderabad, India

3.Feb 2013: Outstanding Presentation of a Research Poster Award in “National Science Day” at Indian Institute of Science Education and Research – Pune, India

4.May 2013: One of the top 12 best Research presentations among ~250 participants from various institutes, for Poster presentation at National centre for cell science (NCCS), University of Pune, India

5.Jan 2012: Recipient of a Senior Research Fellowship from Council of Scientific and Industrial Research, India.

6.Mar-2010: Gate 2010 with 97.60 percentile and all India 127th rank conducted by Indian Institute of Technology, Roorkey

7.Dec 2009: CSIR-UGC-Junior Research Fellowship conducted by Council of Scientific and Industrial Research, India

8.Mar-2008: Gate 2008 with 98.60 percentile and all India 86th rank conducted by Indian Institute of Science, Bangalore, India

9.June-2005: CGPA of 9.46 out of 10.00 with Exemplary in supra – molecular chemistry at School of Chemistry, Bharathidasan University, India

10. Aug-2005: Research internship as a Junior project fellow at Radio Chemical Laboratory, Indira Gandhi center for Atomic Research, Department of Atomic Energy, India

Research Experience:

Project 1: Electrophilic small molecules for the identification of high-quality covalent chemical probes,) 

Project 2: High-throughput screening to identify therapeutics for the enhancement of oligodendrocyte formation form induced pluripotent stem cells and studying their downstream mechanisms

Representative publications:

1. Zita Hubler*, Dharmaraja Allimuthu*, Matthew Elitt, Ilya Bederman, Elizabeth Schick, Eric Garrison, Mayur Madhavan, Molly Karl, Daniel C. Factor, Zachary Nevin, Kevin Allan, Matthew Thompson, Yuriy Fedorov, Franz Bracher, Robert H. Miller, Paul J. Tesar, Drew J. Adams, Accumulation of ∆−8,9- unsaturated sterols enhance oligodendrocyte formation and remyelination. Nature (2018, 560, 372- 376 (*Co-first authors) 

2. Olga Gorlenkova, Kyle Cole, Corey Emerson, Dharmaraja Allimuthu, Marcin Golczak, Phoebe Stewart, Eranthie Weerapana, Drew J Adams, John Mieyal, “Novel Chloroacetamido Compound CWR-J02 is an Anti-Inflammatory Glutaredoxin-1 Inhibitor” PLoS ONE (2017, 12, e0187991)

3. Dharmaraja Allimuthu, Drew J Adams, “2-Chloropropionamide as a low-reactivity electrophile for irreversible small-molecule probe identification” ACS Chemical Biology (2017, 12, 2124-2131) (Citation: 02) 

4. Dharmaraja, A, T*, “Role of reactive oxygen species in therapeutics and drug resistance in cancer and bacteria” Journal of Medicinal Chemistry (2017, 60, 3221-3240). (Citation: 31)

Abstract:

Traditional drug discovery approaches involving screening of small molecules in various cellular phenotypes and subsequent mechanistic investigation have identified numeroustherapeutics. In addition, research directions capable ofrapidlyenabling the understanding of important mechanistic nodes in disease phenotypes or the mechanism of action of therapeutics in disease modelscould accelerate the translation of drugs commercialization. In this presentation, I will discuss two-distinct drug discovery strategies: 1). Chemogenic screening and 2) Activity-based protein profiling (ABPP). In the chemogenic screening, we have utilized a library of 3,000 bioactive small molecules that are either FDA approved or have known annotated drug targets to identify therapeutic agents capable of enhancing oligodendrocyte formation in a disease model of Multiple sclerosis (MS), a demyelinating neurological disorder. Target mapping and studies on the mechanism of action of the lead molecules uncovered the inhibition of enzymes in cholesterol biosynthesis and accumulation of 8,9-unsaturated sterols (Nature, 2018). In the second approach, a library of 300 electrophilic small molecules were synthesized and screened in ABPP to identify high-quality covalent chemical probes. 2-Chloropropionamide is one of the multiple class of electrophilic small molecules, which showed a low-reactivity towards thiol nucleophiles thereby negating potential off-target reactivity. We have identified CW3554-a selective,irreversible inhibitor of protein disulfide isomerase, a protein implicated in the progression of cancer and neurological diseases such as Huntington’s disease (ACS Chem Biol, 2017). Following this, I will present my future research plans on developing novel covalent chemical probes to (i) uncover novel drug-targets in drug-resistant cancer, (ii) selective and irreversible inhibitors of proteins involved in redox-biology and (iii) small molecule mediated degradation of disease-relevant proteins selectively. All this proposed research projects will strongly integrate my expertise in chemistry and biology.

 

References:

1. Schenone, M., et al., Target identification and mechanism of action in chemical biology and drug discovery, Nat. Chem. Biol., 2013, 9, 232-240.
2. Najm, F., et al Drug-based modulation of endogenous stem cells promotes functional remyelination in vivo. Nature, 2015, 522, 216–220.
3. Hubler, Z., Allimuthu, D., et al Accumulation of 8,9-sterols drives oligodendrocyte formation and remyelinaiton, Nature,2018, 560, 372-376.
4. Niphakis MJ, Cravatt BF., Enzyme inhibitor discovery by activity-based protein profiling,Annu. Rev. Biochem.,2014;83:341
5. ‑Allimuthu, D, Adams, D. J., Chloropropionamide As a Low-Reactivity Electrophile for Irreversible Small-Molecule Probe Identification, ACS Chem. Biol., 2017, 12, 2124-2131.

BT Office

Department of Biotechnology

Bhupat and Jyoti Mehta School of Biosciences

IIT Madras, Pin - 600 036

Phone : 044-2257 4100

Email : btof...@iitm.ac.in

[Office Biotechnology]

Dear all,

You are cordially invited for a Special Seminar as per details given below:

Speaker:

Dr. Sachin Kotak, Assistant Professor and Wellcome / DBT Intermediate Fellow, Department of Microbiology & Cell biology, IISc, Bangalore

Date:     30-8-2018

Time:     3:30pm

Venue:   BT Seminar Hall

Title: A Biochemical tug-of-war between Cdk1 and PP2A orchestrate spindle orientation in human cells

Abstract: Proper orientation of the mitotic spindle during metaphase is critical for correct cell division. A flawless division plane is essential for proper tissue morphogenesis as well as in the context of stem cell lineages. In metazoans, correct orientation of the mitotic spindle is governed by an evolutionarily conserved cortically anchored ternary complex comprising of Gai/LGN/NuMA in humans. The ternary complex interacts with the minus-end motor protein complex dynein and thus helps to anchor dynein at the cell cortex. It is the activity of the cortically anchored dynein on the astral microtubules that generates pulling forces which result in the alignment of the mitotic spindle in 3-Dimension cellular space. We have previously shown that NuMA, an essential mitotic protein and a part of the ternary complex is phosphorylated by Cdk1 at the T2055. Interestingly, only non-phosphorylated NuMA at T2055 is enriched at the cell cortex in metaphase, and such non-phosphorylated T2055 NuMA is responsible for the proper spindle orientation during metaphase. To understand how non-phosphorylated NuMA species is generated in metaphase, we have conducted an RNAi-based screen to discover the PP2A holoenzyme that interacts and de-phosphorylates NuMA at T2055. RNAi-mediated loss of PP2A complex causes loss of cortical NuMA/dynein and impact spindle orientation. Addition, we have uncovered molecular mechanisms by which PP2A complex recognize NuMA and de-phosphorylates it at T2055. In summary, our study enlightens a novel pathway by which Cdk1 and PP2A-phosphatase complex orchestrate cortical dynein levels in a spatiotemporal manner for accurate mitosis.

[Office Biotechnology]

Dear all,

This is a gentle reminder for tomorrow's special seminar

at 11 am in BT seminar hall.  All are welcome.

BT Office

Department of Biotechnology

Bhupat and Jyoti Mehta School of Biosciences

IIT Madras, Pin - 600 036

Phone : 044-2257 4100

Email : btof...@iitm.ac.in

---

From: Office Biotechnology
Sent: Friday, August 24, 2018 10:58 AM
To: Office Biotechnology; Head Biotechnology; Amal Kanti; Anju Chadha; Athi Narayanan N; Baskar R; Chandraraj K; Gopala Krishna A; Guhan Jayaraman; Hamsa Priya Mohana Sundaram; Himanshu Sinha; Karthik Raman; Karunagaran D; Kesavan V; Madhulika Dixit; Mahalingam S; Manoj N; Michael Gromiha M; Rajamanickam Murugan; Nitish R Mahapatra; Rama Shanker Verma; Sanjib Senapati; Sathyanarayana N Gummadi; Smita Srivastava; Srinivasa Chakravarthy V; Subramaniam K; Suraishkumar G K; Suresh Kumar Rayala; Vani Janakiraman; Vignesh MuthuVijayan
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Subject: Special seminar invitation

 

[Subramaniam K]

Gentle reminder…..

 

From: Office Biotechnology
Sent: Friday, August 24, 2018 12:38 PM
To: Office Biotechnology; Head Biotechnology; Amal Kanti; Anju Chadha; Athi Narayanan N; Baskar R; Chandraraj K; Gopala Krishna A; Guhan Jayaraman; Hamsa Priya Mohana Sundaram; Himanshu Sinha; Karthik Raman; Karunagaran D; Kesavan V; Madhulika Dixit; Mahalingam S; Manoj N; Michael Gromiha M; Rajamanickam Murugan; Nitish R Mahapatra; Rama Shanker Verma; Sanjib Senapati; Sathyanarayana N Gummadi; Smita Srivastava; Srinivasa Chakravarthy V; Subramaniam K; Suraishkumar G K; Suresh Kumar Rayala; Vani Janakiraman; Vignesh MuthuVijayan
Cc: bt0...@googlegroups.com; bt20...@googlegroups.com; bt2014s...@googlegroups.com; bt1...@googlegroups.com; bt20...@googlegroups.com; bt1...@googlegroups.com; bt1...@googlegroups.com; bt1...@googlegroups.com; o201...@googlegroups.com; bt2...@googlegroups.com
Subject: Special seminar invitation

 

Dear all,