INDIA / California, USA :
This is the seventh part of the series called `Scientist Says’ where we bring for our readers the significant and commendable research works of young scientists.
Dr. Mohammed Kausar Raza completed his M.Sc. in Inorganic Chemistry from Jamia Millia Islamia, Delhi and began his Ph.D. in the year 2015 with Prof. Akhil Chakravarthy lab, Inorganic and Physical Chemistry Dept., IISc, Bangalore. After completing his Ph.D in the year October 2019, he joined California Institute of Technology (Caltech) in the United States as a postdoctoral research fellow in January 2020. He shares his significant research works with Rashida Bakait of India Tomorrow. Here are the excerpts of the interview.
Q. Please give a brief explanation of your research.
Ans. My research interest mainly focuses on to locate the lesions with the help of [4Fe4S] cluster and their treatment using Pt-based anticancer agents. The research area is divided into two parts: (i) Investigating the chemical role of [4fe4S] cluster in eukaryotic proteins through electrochemical and biochemical studies. (ii) Use of Pt-based complexes for chemo phototherapeutic treatment of cancer.
Cancer is considered as one the deadliest diseases which has been outspreaded in various parts of the human body. Various methodologies have been implemented till date to fight against the proliferation of cancerous cells, namely, Chemotherapy (mainly Pt-based anticancer drugs), Photodynamic Therapy (which involves photosensitizer, light, molecular oxygen), etc. To fill the pitfalls of the conventional chemotherapeutic and photodynamic therapeutic drugs including the NER machinery and less tissue penetration respectively, during my PhD research at Indian Institute of Science, Bangalore, I combined these two well known modalities, i.e.; chemotherapy and photodynamic therapy (PDT) by tuning the structural properties of Pt-based complexes to kill the cancer cells selectively. The idea was to develop the series of conjugates bearing the structural framework as of the conventional chemotherapeutic anticancer drug, cisplatin and BODIPY dyes for PDT activity. In photodynamic therapy, the growth of cancer cells can be terminated in the presence of light which generates ROS (reactive oxygen species) capable of cleaving the DNA of the tumor cells and in turn causing the cell death. The cell imaging is beneficial to track the anti-cancer drug inside the body. The combination of the Pt metal which encrusted the path for DNA cross-linking and the BODIPY motif attached which aided in cell imaging and killing of cancer cells in the presence of light, comes out as a new scope to design the more efficient photodynamic chemotherapeutic anticancer agents.
Earlier in my PhD, I have made efforts to treat the cancer, now I am exploring my research to detect the lesions through DNA mediated charge transport chemistry. It focuses on assessing the functional role of iron sulfur [4Fe-4S] in eukaryotic DNA replicative and repair proteins. We perform the electrochemical investigation to detect the tumor/disordered sites using DNA mediated electron transfer.
Q. When did you begin and complete your research?
Ans. My research started with my master dissertation work in the year 2014. I started working as a PhD researcher in the January 2015 and successfully submitted my thesis in Oct. 2019. Now, I have been doing research as a postdoctoral fellow in the field of biochemistry since January 2020.
Q. What was the objective of your research?
Ans. Since a variety of anticancer drugs are known to treat numerous kinds of cancers, namely colorectal cancer, breast cancer, oral cancer, and lung cancer etc. My aim was to design and synthesize a drug in such a way which is highly selective towards killing the cancer cells without harming the normal living cells. We intended to approach a dual action mechanism of platinum based anticancer drugs for real time tracking and selective cancer cell death.
Q. What were the findings of your research?
Ans. We prepared a series of mono-functional Pt-based complexes capable of binding with DNA for the treatment against cancer. We have mainly designed the mitochondrial targeting anticancer drugs, as mitochondria is known as the powerhouse of the cell and it lack NER machinery. Major outcome of our studies is in the form of a indigenously synthesized prodrug which have 100-fold better anticancer activity than FDA approved Photofrin drug. Moreover, this drug can be tracked inside the cell which is not the case with any of the FDA approved platinum based anticancer drugs. We have conducted the in-vivo anticancer studies of these drugs in the living mice models using photodynamic chemotherapeutic dual action mechanism and obtained promising results which is turned out to be a patent in this emerging field. This work was done with the collaboration in the department of biological sciences at IISc.
Q. What was the conclusion of your research?
Ans. My work presents a thorough investigation on the Pt-based anticancer drugs derived from cisplatin motif. Appendment of BODIPY moieties as florescent probes aided in cell imaging and production of ROS to kill the cancer cells in presence of light. The in-depth photophysical investigation of our Pt based complexes revealed their properties to absorb visible light and made them suitable for real time tracking. This study provides further scope for combinatorial research that includes photodynamic therapy and DNA cross linking ability of the monofunctional Pt (II) drugs (chemotherapy) against cancer. Finally, the in vivo assay results on mice showed significant arrest of tumor growth and its shrinkage in size thus giving new insights in the chemistry of platinum-based PDT agents.
Q. What kind of challenges did you face?
Ans. In my masters, I have pursued a research project in coordination chemistry. I have learned various synthetic procedures to synthesize a variety of transition metal complexes and carried out an in-depth characterization using various spectroscopic techniques. Then I joined a bioinorganic chemistry lab, where the challenge was to design the metal complexes with a sharp focus on its pharmacology (pharmacokinetics) by implementing a cost-effective methodology. Also, the fluorophore motifs incorporated in the structure must have the significant absorption and emission photophysical properties which can aid the drug in penetrating deep inside the body. It was achieved after studying the UV-Vis properties of the drugs. Developing a drug performing a dual action mechanism in treating cancer cells was itself a challenge. Furthermore, I joined a biochemistry lab at Caltech, moving from bioinorganic to biochemistry was another major challenge, where I had to learn the new techniques and methods prior to performing the experiments and analyzing the outcomes.
Q. Any scholarships or awards for research?
Ans. As the recognition of my doctoral work, I received the prestigious Carl Storm International Diversity (CSID) fellowship for Gordon Research Conference (GRC), Metal in Medicine, USA. I am also a recipient of “Government of India International Travel Research Award (DST), CSIR Travel Research Award, ICMR Travel Research Award, SBIC Student Travel Grants for ICBIC-19 in Interlaken, Switzerland. I received fellowship from MHRD and CSIR for the five year during my Ph.D.
Q. How do you think your research would be beneficial to the society or industry?
Ans. Cancer counts among the second deadliest diseases in the world. Among all types of cancer, about 30% of India’s affected population accounts for oral cancer only. Among the various therapies established for cancer treatment, photodynamic therapy is well known for the treatment of oral cancer. My research on Pt based drugs will provide a new insight and scope to combine the two therapies and kill the tumor with notable potency. Our mice model demonstrated an excellent efficacy of our drug inside the living being. These new findings can lead to investigate the drug-tumor interaction inside the human body. Implementation of our Pt based prodrugs will provide a new way to treat the cancer. Moreover, commercializing these drugs may reduce the cost of treatment. In addition, it’s manufacturing at industrial level will increase the employment for several educated and skilled people in our country.
Q. Any new research you are working on now?
Ans. Currently, I am working on the DNA mediated charge (electron) transfer chemistry. My aim is to investigate the rapid communication among DNA-processing proteins for repairment through DNA-mediated redox signaling. These DNA-processing enzymes bear an iron-sulfur [4Fe4S] cluster which performs common redox switch on binding with DNA and gives rise to DNA-charge transport chemistry. It mainly focuses on the electrochemical investigation of the chemical role of the [4Fe4S] cluster in eukaryotic DNA primase and the polymerase. Importantly, electrochemistry on the DNA-modified electrodes facilitates reaction under aqueous, physiological conditions with a sensitive electrical measurement of binding and activity.
Q. How do you think your research can be carried forward?
Ans. Organelle targeting is an emerging field and needs thorough investigation to study the action of metallodrug inside the biological systems. Introducing selectivity in structural framework of the drugs towards single organelle targeting can make the drug more potent and viable. Other metals are also prominent on anticancer platform, so it is possible to design and synthesize such cost effective and biocompatible metal ligand frameworks which is capable of performing multiple actions with significant potency. The preliminary in vivo results and pharmacokinetics suggested that a detailed study need to perform so that it can be taken to clinical trial.
Q. Give some suggestions to the budding scientists.
Ans. Academia is a never-ending journey full of exciting adventures. It should be spent with utmost pleasure and satisfaction while enjoying science. One should be able to eminence both the personal affairs and professional business. Be clear and rational. Do not hesitate while expressing and talking about yourself, be it stress or mental health imbalance. Also, create another world outside the lab and explore it. Hone your communication skills. In academia, communication is the key to success Always indulge in a teamwork, moreover, in order to be an interdisciplinary scientist, be open to accept and request for collaboration. Do something different which no one thinks is important and invest your efforts and time in it. Learn broadly. Be bold. Be passionate. Establish a name for yourself. Above all, perhaps, to be successful in academia you need to develop your persistence and preserve your creativity no matter what. The key to unlocking the untapped potential is to create and build a path conducive to novelty in science. Make your research plans wisely and execute them in a disciplined way. Always remember, slow and steady wins the race.
source: http://www.indiatomorrow.net / India Tomorrow / Home> Education / by Rashida Bakait, India Tomorrow / May 01st, 2021