Molecular biologist and biochemist Omar Khan of Hamad Bin Khalifa University is attempting to prevent cancers being resistant to chemotherapy.
Assistant professor Omar Khan graduated with a master’s degree in biochemistry from Karachi University, Pakistan, before moving to Sweden to do another master’s in cell biology in Uppsala University, Sweden.
He then spent five and a half years doing a PhD in molecular medicine under Prof Martin Bergo at the Sahlgrenska Cancer Centre at the University of Gothenburg. This was followed by postdoctoral research under Dr Axel Behrens at the Francis Crick Institute in London, and being an honorary teaching assistant at King’s College London.
Khan is now working at the College of Health and Life Sciences at Hamad Bin Khalifa University, Qatar.
‘Some cancers are difficult to treat and a lot of research has been done to cure them with little to no success – I was not the only one who tried and failed’
– OMAR KHAN
What inspired you to become a researcher?
During my undergraduate studies, I took a course in genomic DNA recombination. I was fascinated by how we can play around with different gene sequences and create mutant species.
For example, during the course, I read that using DNA recombination and molecular cloning scientists were able to create plant species that could resist the harsh and cold temperatures in places like Canada.
I got really excited by those techniques as, somehow, I had the feeling that in the future we might be able to cure lethal human diseases by using similar techniques. I believe the advent of CRISPR/Cas9 genomic editing has provided us the tool to start thinking of ways to do that.
Can you tell us about the research you’re currently working on?
Early in my career I was exposed to post-translational protein modifications and how they can activate or inhibit protein function. Ubiquitylation is one of the most abundant post-translational protein modifications and every single protein undergoes it among thousands of proteins in our cells.
So, ubiquitylation is an important modification to study. Basically, I was focused on finding a drug target that could help patients with cancer, more specifically, pancreatic or colorectal cancer.
Initially, I lost the first couple of years of my postdoctoral training chasing my dream to find a novel cure for pancreatic cancer with no success at all. But the lesson I learned was that some cancers, such as pancreatic cancer, are difficult to treat and a lot of research has been done to cure those cancers with little to no success, so I was not the only one who tried and failed.
Finally, I found my niche in studying the molecular details of how the tumour suppressor protein FBW7 is regulated in normal and cancerous cells, given the fact that loss of function mutations in the FBW7 gene can make some cancers resistant to chemotherapy.
This was an exciting new direction for me with ubiquitylation of FBW7 and its substrates as a major focus. We never thought that this would lead to the discovery of a potential drug target. But, to our surprise, if we inhibit this negative regulator of FBW7 protein, we could enhance FBW7 function and sensitise cancer cells to chemotherapy without affecting the normal cells.
Now my lab here in CHLS at HBKU Qatar will study the biology of this new drug target and evaluate the suitability of blocking this protein in colorectal cancer.
In your opinion, why is your research important?
I believe ubiquitylation is found in almost every cellular process you can think of. We are now moving forward from the most widely accepted notion that ubiquitylation is just marking proteins for proteasomal degradation.
There are numerous discoveries lately that show that ubiquitylation controls diverse cellular processes including immunity, DNA damage response, cell cycle and replication stress. All these processes are, directly or indirectly, connected to several human diseases.
Often, major breakthrough findings in biology come from the study of basic concepts in molecular biology. My lab’s focus on colorectal cancer with respect to ubiquitylation and the newly identified protein that also happens to be an E3 ligase aims to understand the role of this gene in stem cell maintenance, differentiation, and tumour growth in mammalian gut.
In addition, we plan to functionally characterise every single E3 ubiquitin ligase in the mammalian genome. One unappreciated advantage of working with E3 ubiquitin ligases is that, since they are protein enzymes, they are drug-able, providing an opportunity to capitalise in the event of a novel target discovery.
What are some of the biggest challenges you face as a researcher in your field?
As a cancer biologist, I feel chemotherapy resistance is the biggest challenge to tackle. Why some cells become resistant to chemo or radiotherapy while other cells die is not so clear.
There are a few proposed mechanisms, but the challenge is that there are multiple pathways to achieve the same thing and one mechanism may not work in all cancers. Even intra-tumour heterogeneity within the same cancer may have multiple resistant clones.
Are there any common misconceptions about this area of research?
Social media has its pros and cons. Nowadays it’s very easy to spread a rumour or fake news without even checking the validity of the claim. Sometimes I get funny videos or articles forwarded to my WhatsApp account, with claims that a cure for cancer has been found in a unique fruit and that scientists want to hide this from the public because of commercial gains.
Spreading these ludicrous claims with no authentication is a dangerous precedent. I think we as scientists have a responsibility to convey scientific discoveries, knowledge and progress to a general audience.
Each one of us should be connected to our community and at least once a year give a lecture to the general public on topics such as: What is cancer? How does it spread? What is a tumour suppressor? How do we treat cancer? Why is it so difficult to treat cancer? And of course, why this mysterious fruit might not be the cure for a cancer patient.
What are some of the areas of research you’d like to see tackled in the years ahead?
Enhancing the tumour suppressor function of certain proteins to suppress tumour cell growth is one area of continuous advancement that I believe is a very exciting prospect for cancer treatment.
I would love to see drugs in the market that can restore tumour suppressor protein 53 activity or FBW7 activity to either block the progression of cancer or sensitise cancer cells to chemotherapy.
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