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Differentiation Therapy: A Cure For Childhood Cancer?

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How can differentiating cancerous cells help researchers come up with a better cure for certain cancers? To find out, we spoke to Dr Pierre Schembri-Wismayer, a man who has dedicated many years of his life to researching a revolutionary kind of cancer therapy.

pierre schembri wismayerAccording to Dr Pierre Schembri Wismayer, there are two types of cancer in the world: the ones that are instigated from repeated exposure to toxins (‘Outside’ cancer), and the ones that develop randomly in both children and adults (‘Inside’ cancer), which include brain, blood and bone cancer.

As a senior lecturer at the University of Malta’s Department of Anatomy, Faculty of Medicine and Surgery, Dr Pierre Schembri-Wismayer has spent years working on a cure for the latter; a cure that can differentiate immortal cancer stem cells from mortal cells.

“Although different cancers require different treatments, all the cures we have so far can be destructive as well as beneficial,” explains Dr Schembri Wismayer. “Excluding surgery, which is still invasive, chemotherapy and radiotherapy can be quite harmful to the body… In fact, people undergoing these therapies tend to lose their hair, feel sick, and contract more infections.

“Moreover, normal cells grow old and die naturally while most cancer cells are constantly in their adolescent phase, meaning that, as a person grows weaker from the disease, the cancer cells inside their body grow relatively stronger.”

Then, 20 years ago, research revealed that this process could be reversed in certain cancers that afflict both adults and children. It was a groundbreaking theory, and one that has since been proven to be a valid candidate for cancer therapy.

 “Differentiation Therapy is something I began researching when I was doing my PhD, and I’m still very involved in this. In fact, I’m currently on a two-year sabbatical so as to focus more on its workings,” Dr Schembri Wismayer tells us. “One of the ideas I’ve had with regards to this was to look at some of the world’s natural differentiating systems to see how cell behaviour there could help us differentiate cancer.”

Dr Schembri Wismayer knew that in certain animals, such as salamanders and starfish, when one of their limbs is cut off, the cells stem cellsaround the wound start to regrow the missing arm or leg.

“Thus effectively reproducing the muscles, bone and skin that had been lost. This is differentiation, where stem
are becoming adult (or older) cells of various tissue types,” he says.

“The signals that these stem cells received were clearly instructing them to become adult and fully differentiated tissues when needed – these animals don’t grow a spare leg all the time, just when they need to. And since cancer cells are like stem cells, in that they can do or be various things, then instructing them to grow old and die using these same signals didn’t seem so far fetched!”

The best part about Differentiation Therapy, however, isn’t the fact that it can cure cancers more easily than other treatments, but that it can do so without harming the healthy cells.

“For the first time, instead of injecting chemicals into a patient’s body and hoping that they will kill more cancer cells than healthy ones, we can now be sure that the cure will only kill cancer cells by forcing them to grow old, and die naturally,” he adds.

Although this cure is not available yet for most cancers, it has come a long way in the past 20 years and it will, hopefully, offer patients of all ages – including children – a chance for survival against various kinds of ‘Inside’ cancer, including bone and brain cancer in the not too distant future.

“‘Outside’ cancers are cancers that develop over time from repeated DNA damage from toxins and are therefore almost never seen in children. These include skin, lung and colon cancers, and require a completely different treatment to the Differentiation Therapy,” explains Dr Schembri Wismayer. “In fact, here we focus our research on immunotherapy.”

The difference between those that can be treated using Differentiation Therapy and those that cannot, is that of one single random driving mutation being largely responsible for the cancer. In fact, it is this random gene defect that allows the research team to target cancer in children. Even so, medicine and research are advancing at an unprecedented rate. Acute promyelocytic leukemia (APL), which was 100 per cent incurable 20 years ago, is now 90 per cent curable! So there is a lot of hope in this sphere.

AliveUnsurprisingly, this research has gained a lot of interest from the public and NGOs, including the Alive Charity Foundation, who has specifically chosen research in Differentiation Therapy as one of the beneficiaries of this year’s cycle challenge.

 “Alive’s donation will help us fund a PhD student to focus on childhood cancers of the brain, blood and bone, and to provide a new pair of able hands to the team,” says Dr Pierre.

“He or she will also be able to go on a short-term scientific mission through the European Consortium, StemChem, and gain invaluable knowledge and techniques that will be able to help us further our research in Differentiation Therapy, especially in brain tumour research, which is a relative new area for us,” Dr Pierre concludes.

If you would like to join the Alive Charity Foundation team to raise funds for research in aid of Children Cancer click here.

You can be part of this fascinating world of research by helping many other researchers achieve their breakthroughs in all the faculties of the University of Malta, including medicine, archaeology and technology. Please click here for more information on how to donate to research of this kind through the Research Trust (RIDT).


The KLF1 Gene – A Maltese Discovery

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Dr Joseph Borg

What is genetic behaviour? And how does understanding its workings help researchers find cures for diseases? Here we chat to Dr Joseph Borg, the man who first discovered the existence of important DNA mutations in the KLF1 Gene.

Most of us have a basic understanding of what DNA is and how it affects our biology. What most of us may not know, however, is just how powerful its influence can be in terms of diseases.

Over the years, in fact, researchers have discovered that not only does DNA determine our eye colour and height, but it is also coded in a way that can predispose us to many ailments, including various kinds of cancer, complex disorders (such as Parkinson’s disease and Diabetes Mellitus Type 2) and classic disorders (such as thalassaemia and cystic fibrosis).

But DNA is not just something you’re born with; it’s something that changes as you grow older and according to the environment you’re exposed to.DNA

“A very important influence on DNA is where you live, what you eat, where you work and even epigenetics (how different environmental influences affect DNA),” explains Dr Joseph Borg, an academic lecturer for the Department of Applied Biomedical Science within the Faculty of Health Sciences at the University of Malta.

“Some genetic disorders, such as thalassaemia, haemophilia and cystic fibrosis, you’re born with, while others, like diabetes, dementia or Alzheimer’s, you develop as a result of the environment you live in and other predisposing factors that includes genetics,” he adds.

Joseph first became interested in genetic behaviour while reading for his B.Sc(Hons) degree at the University of Malta, and, although he graduated in 2004, he has remained active in this field of research.

“There are five main areas in biomedical science research,” he explains. “Haematology (the study of blood and blood-related diseases), histopathology (the study of tumour and cancer biology), microbiology, biochemistry, and blood transfusion science and immunology, which often go hand-in-hand.

“I found all this incredibly fascinating; so much so that my B.Sc thesis was on the genetics of coeliac disease in Malta. But I have to admit that I got more than I had bargained for in my undergraduate work…

behavior-genetic-basis-of-3887“Besides working in the laboratory to conduct genetic testing, I was also introduced to clinical research dealing in and discussing what I was researching with certain recruited participants for the project.

“It turned out well, however, and I continued using that model throughout my Masters and PhD,” he explains. “In total, the research took six years, and it was at the end of that period that I discovered a genetic mutation that had been previously unknown.”

The Krüppel-like factor, or as it is more commonly known, the KLF1 gene, was discovered through DNA sequencing, which is when the DNA is stripped down to single, molecular level.

“It was all rather coincidental, really,” Joseph explains. “Every child born is tested for abnormal haemoglobins (the red proteins responsible for transporting oxygen through the blood), and, when we identified a mother and her newborn with abnormally high levels of foetal haemoglobin, we decided to test her immediate family.

“Through that we discovered that in an extended family of 27 members, 10 of this woman’s kin had the same abnormally high levels of foetal haemoglobin, and further research revealed that the gene that codes the haemoglobin molecule in the foetal haemoglobin (which is usually switched off at birth) was still on and intact!”

This was a eureka-moment for Joseph, and it has since paved the way for further research into how certain diseases could be cured in the future. Internationally it was also a turning point and researchers as far away as in Australia and Asia are now building on what Joseph had initially discovered about the KLF1 gene.

“Presently, we’ve identified some different mutations and the ways in which these control the functions of the hemoglobinhaemoglobins,” says Joseph. “So far, we’ve discovered that these genes may not always affect haemoglobins as it was first assumed.

“Now we’re actively studying that, and we’ve realised that the KLF1 gene is not the sole gene that controls this haemoglobin switch, so we’re looking for the other genes and tandems which may be having a similar impact. Even so, this will take time, and we’re at a point where we’re sifting through many gigabytes-worth of data.”

But how does this affect the general public?

 “Each person’s DNA is unique, and that means that we respond differently to things,” Joseph explains. “Personalised medicine and treatment is the future of medicine and it is only through the research of the genes in DNA that we can truly boost pharmacogenetics (the study of how inherited genetics can affect the way our bodies react to drugs and medicine) and make strides forward on this front.”

You can be part of this fascinating world of research, by helping many other researchers achieve their breakthroughs in all faculties at the University of Malta, including medicine, archaeology and technology. Please click here for more information on how to donate to research of this kind through the Research Trust (RIDT).

The Mobile Dental Clinic – Behind the Scenes

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The University of Malta’s RIDT-funded mobile dental clinic will be hitting the roads in just a few weeks time. To celebrate this milestone, we spoke to Albert Bonnici, the engineer who has turned a regular truck into a state-of-the-art dental centre.

RIDT +ö+ç+¦ Mobile Dental Unit progress +ö+ç+¦ visit by UOM Rector 2404150004

Can you imagine life without teeth? How would we chew our food? What would we look like when we smiled?

Yes, teeth are incredibly important, but many of us take them for granted and, unless we have a toothache, we often neglect to visit the dentist. How widespread is this attitude? How much do we care about our oral health?

To address this, Malta’s first-ever mobile dental clinic will – soon – start its journey through the streets of Malta, visiting not only those who are unable to leave their homes, but also schools and community centres. Its on-board specialists will give advice, perform check-ups and emergency procedures on the spot, while gathering crucial data and disseminating related information.

But who built this fantastic vehicle, and what did it involve?

Engineer Albert Bonnici

This is the story of engineer Albert Bonnici, in his own words:

“I was approached about this project after Professor Nikolai Attard, the Dean of the Faculty of Dental Surgery, explained his brilliant idea of getting the Maltese community together (with the help some of sponsors) to promote dental health,” says Albert. “This inspired me, and I started thinking about the ways I could help bring the project to fruition.

“The first step was to get the best base unit available,” he explains. “I ended up with a very suitable DAF 45 LF cargo truck that had a 6m x 2.4m working space and a hydraulic tail lift.

“Obviously, the medical functions were my number one priority, but mobility, ergonomics, eco friendliness and, last but not least, radiation, and health and safety standards also had to be given their due importance from the initial stages.

“Designing the basic interior layout was left to the Faculty of Dentistry, while I did the rest, which included sizing, selecting and fitting the equipment and services, both on the inside and the outside the truck,” he continues.

DSCF5799“These included electrical power circuits and pipework for compressed air, vacuuming, hot and cold water, and drains,” he explains. “A hydraulic vehicle stabiliser unit also had to be installed under the chassis, while water tanks, pumps and an air conditioner were fitted to the sides.

“Then came the interior design stage,” he tells us excitedly. “Thermal insulation, cabin structure, panelling, flooring and furniture are just a few of the tasks that had to be completed before the medical equipment could be installed.

“The actual work started late in the summer of 2014, though planning had to be done quite some time before that date,” he continues. “At the moment, the project is at an advanced stage with the important finishing touches to complete, including related exterior artwork to suit.

“It wasn’t all a breeze, however” Albert says. “Financing was quite an issue at first, though, thanks to a number of sponsors, we reached our goals.

RIDT +ö+ç+¦ Mobile Dental Unit progress +ö+ç+¦ visit by UOM Rector 2404150030

“Even so, the biggest issue was allocating time on my part… Working single-handedly for most of it meant I spent about one day per week on this project, and this resulted in certain tasks taking longer than expected.

“I have to admit, however, that although each minor job came with some sort of satisfaction, the cherry on the cake was the interior décor! It’s not my forte, granted, but switching on the LED soffit lights once most of the interiors were finished revealed a five-star clinic that, in my humble opinion, looks great!” Albert concludes.

Help us fund more projects like this as well as research in all the faculties including medicine, archeology, technology and many other spheres, by donating to RIDT. Click here for more information on how to donate.