‘We Have Found Three Inhibitors That Reduce Pain During Cancer’

Dr Muzaffar A Macha has been a ‘golden boy’ throughout. At AIIMS and abroad and now home as head of IUST’s Watson-Crick Centre for Molecular Medicine, after working extensively on head and neck cancers, he has been able to identify an antidote for managing the excruciating pain during all cancers. In a freewheeling conversation with Masood Hussain, the young scientist talks about his research career and the immediate goals he has set for himself and the centre

KASHMIR LIFE (KL): How was your journey from Kashmir to the USA and then back to Kashmir?

 DR MUZAFFAR A MACHA (MAM): I have done my schooling at Madrassa Taleem-ul Islam (MTI), Tral.  Then I did my bachelor’s in Biochemistry and Environmental Sciences from SP College Srinagar. After that, I went to the Jamia Hamdard for my master’s, which I completed in 2005. I topped there and also received a gold medal.

Then, I applied to various universities including Jawaharlal Nehru University, All India Institute of Medical Sciences, Indian Institute of Science, CCMB Centre for Cellular and Molecular Biology, and Centre for DNA Fingerprinting and Diagnostics for PhD. I was selected by three Universities, but I choose AIIMS, because of my personal preference and because of the good translational (applications to humans) research work that was being carried out at AIIMS.

There, I joined the laboratory of Dr Ranju Ralhan. Then I was shifted to another mentor, Sham Singh Chauhan who is the head of AIIMS’s biotechnology department.

I completed my PhD in 2010 and was awarded with a Gold medal called Gita Mittal Award for the best PhD student with the best publications. My PhD work was mostly about head and neck cancer.

After that, I went to the University of Nebraska Medical Center for my post-doctorate. There, I joined Dr Surinder Batra, a scientist and a pancreatic cancer specialist. I worked extensively there on cancer biology. Since I had worked on head and neck cancers during my PhD, because of the fact that India has the most cases of this cancer, I started a group to work further on this.

We continued to work for four and a half years till the completion of my Postdoc. After that, I was inducted there as an Assistant Professor in the same department. I continued there until 2019 and moved back home because of certain family reasons and eagerness to serve my own society.

After coming back, I applied for the Ramanujan Fellowship and Ramalingaswamy Fellowship and I was selected for both fellowships. I joined the Central University of Kashmir (CUK) as a Ramanujan Fellow.

A year after working there, I moved to the Watson-Crick Centre for Molecular Medicine of the Islamic University of Science and Technology (IUST). Soon joining as a Ramalingaswami fellow, I was selected as an Assistant professor for Molecular Medicine in the Centre. Presently I am heading the centre.

KL: Cancer is among the most life-threatening diseases. Where the science is right now in the understanding of cancer?

MAM: In the last 10 years, the technology that has emerged to identify cancer, to know the cause of cancer and to understand the basic molecular biological concepts proved to be useful and convenient. To a very large extent, we have conquered the battle against cancer. The immunotherapy that is often used these days is yielding good results in treating cancer. Recent studies and clinical trials all over the world proved that immunotherapy is good among all methods for treating cancer.

The Awantipora Molecule

KL: You have worked extensively on Head and Neck Cancer during your PhD. What were the major takeaways from the research?

MAM: As per the studies and statistical data, India has a huge consumption of tobacco products. Head and neck cancer is mostly because of the consumption of tobacco-based products. My research project during my PhD was based on “How cancer is caused by the consumption of Tobacco based products?” I identified cancer development at the molecular and cellular levels. I identified the novel signalling pathways that get activated and lead to cancer.

Along with this, I identified the usage of natural compounds like Curcumin and Guggulsterone to nullify the effects of smokeless tobacco. These compounds can largely reduce the effects of cancer-causing smokeless tobacco.

KL: Has there been any kind of comparative study? I mean is the pattern different for cancers caused by smoking and non-smoking cancer agents?

MAM: It has been studied and is widely accepted all over the world that smokeless tobacco agents mostly cause mouth cancer but smoking usually causes lung cancer. Still, there are cases of people in India and even in Kashmir who have lung cancer even though they had not consumed any smoking or non-smoking product. Thus it is not only the eating habit, which may lead to cancer, although in the majority of cases, it is true but there are genetic causes also. The off-springs of individuals suffering from cancer are more susceptible to cancer because of certain mutations.

KL: Were your findings accepted by the market and what was the response from academia?

MAM: During my PhD days, we ran a clinical trial in the department of biochemistry and the department of head and neck Surgery of AIIMS. Patients with head and neck cancer were given Curcumin and the effects were studied. I found out that curcumin prevents cancer to some extent. It also reduces the size and recurrence /regrowth of cancer.

KL: After completing the successful clinical trials, things usually move to the pharma sector. Is there any such thing based on clinical trials that the market was triggered by your findings?

MAM: In India, clinical trials were done for curcumin and there are even curcumin derivative compounds in the market that are used as cancer-preventive agents. In the advanced and late stages of cancer, these compounds are not effective but they help in preventing the occurrence of cancer at the early stages.

KL: You did your Postdoc in the USA, What was your research about, and what were the major takeaways from that?

MAM: Initially I worked on pancreatic cancer under the mentorship of Dr Surinder Batra. There, I recapitulated the findings of my PhD work, that is how the natural compounds can prevent the development of cancer and decrease cancer-causing active signalling pathways present in head and neck cancer. I attempted to use the same for pancreatic cancer. My other colleague was working on a molecule called Mucin (MUC4). The findings of my PhD proved that Guggulsterone decreases the expression of Mucin/MUC4.

Expression of Muc4 in the cells increases the tendency of having more aggressive and proliferative cancer. My research study was to reduce the proliferation (Metastasis) and aggressiveness of cancer cells using Guggulsterone.

After that, I created a group of dedicated people to study head and neck cancer. I also came to know that MUC4 is expressed in around 90 per cent of cancer patients, and it causes drug resistance against cancer with time. I came to know that MUC4 is an important factor in the development and metastasis of both pancreatic as well as head and neck cancer.

KL: What was the follow-up of your research? You must be in touch with the labs still because the scientific community remains in touch with each other. Has there been any kind of formal movement to what you did during your Postdoc?

MAM: No one worked on the MUC4 for quite a long time, but when I was inducted as an Assistant Professor, I started to work on one more molecule called NR4A2 (a transcription factor). I concluded that this molecule has a major role in causing intense pain during cancer. I along with other colleagues are working to design an inhibitor against it. We have identified three inhibitors and we are going to publish this very soon. Inhibitors reduce pain across all cancer patients to a very large extent.

Besides, we found that the pain in pancreatic cancer due to the Perineural-invasion (i.e., Cancer cells penetrate into the nerve cells), is also because of the NR4A2 molecule and can be cured with the help of inhibitors.

KL: You are currently working at the Watson-Crick Center for Molecular Medicine of the IUST. What is your individual research focus there?

MAM: In Kashmir particularly, gastrointestinal tract cancers like oesophageal cancer, stomach cancer, and colorectal cancer are more common in people among all the cancers. Kashmir has the third highest number of oesophageal cancer patients all over the world after China and some areas of Iran.

Although there has been a lot of research work on colorectal cancer and oesophageal cancer, but the actual biology and high throughput technology have not been used here in Kashmir until now. We still do not have the cell-line models and animal models which are necessary to study cancer.

My current project under the Ramalingaswami Fellowship is to develop in-vitro models in order to better study oesophageal and gastric cancers. These models can be used to study the underlying biology and molecular biology of cancer.

KL: Since your Centre is newly established, what is the present state and status of its infrastructure?

MAM: The Watson-Crick Centre for Molecular Medicine started in 2018 but the faculty recruitment was done in 2020. I along with my colleagues like Dr Rais and Dr Arsheed joined in 2020. We started from zero. There was very little infrastructure around and within less than two years, we achieved a great feat. It is all with the help from the higher authorities at the IUST. We now are at the stage of working at an extensive pace and for longer durations. Earlier we had the limitation of culture rooms here but now we almost have everything to do full-fledged research.

KL: Do you have the limitation of any major equipment because high-end research essentially needs sophisticated machinery?

MAM: We do not have high-end and high-throughput machinery, but we have basic instruments. We have procured many instruments and machines and we are in the process of procuring many other. We have an allotment of around Rs 6 crore of funding grants of which Rs 1 crore is for procuring instruments. Projects that require high-end instruments are mostly being done in collaboration with other departments or are outsourced.

KL: Many times more than one university work on the same research topic, but every university has a different vision and different priority. Is any other institution in Kashmir working on the same topic as you do?

MAM: As such, there is only one scientist at Sheri Kashmir Institute of Medical Sciences working on the in-vitro models, but I do not know what stage has he reached. Importantly it is worth knowing whether you have the expertise for the research or not. During my Postdoc and Assistant professorship, I have personally made many in-vitro models, so I have the expertise to carry forward that work in our Center at the IUST.

.. Mujtaba Hussain processed the interview