A Research Blog

In 2006, Japanese scientist Shinya Yamanaka and colleagues discovered that mature cells can be reprogrammed and reverted to a stem-cell-like state. Known as induced pluripotent cells (iPSCs), these cells have the ability to develop into any cell type. This discovery was stunning enough that Yamanaka was awarded the 2012 Nobel Prize in Physiology or Medicine for his revolutionary work on reprogramming adult cells, and spurred thousands of related publications.Owen

The field of reprogramming has generated a lot of excitement in recent years because iPSCs are a revolution in regenerative medicine, which seeks to replace tissue or organs damaged by disease, trauma, or congenital issues. In addition, reprogramming presents the possibility that we could generate patient-specific cell-types to model disease or use as a cell therapy. However, in order to be able to utilise these cells to their fullest extent, it is important that we fully understand the reprogramming process. To do this we need to study the process starting from many different cell types, not only from a single source. To date, fibroblasts have most often been used as a source cell type for reprogramming simply because they are easy to acquire and manipulate. In other words, fibroblasts was chosen for convenience rather than because of an important biological role in reprogramming. As such, much of what we know about this process is derived from work on fibroblasts and we assume that what we have learned from this conversion also holds true for other cell types.

aspirinAspirin is the poster child for repurposed drugs. It was initially used over a century ago to treat pain, fever and inflammation. In the 1980s, researchers noted that its mild blood thinning side effect was highly effective in preventing recurrent heart attacks and strokes. Now, the interest in aspirin has shifted from cardiovascular to cancer prevention and treatment. In fact, the National Cancer Institute in the United States highlighted the role of aspirin in cancer treatment as one of the most ‘provocative questions’ to answer in 2012.

Multiple studies have shown a link between long-term aspirin use and a reduction in the incidence and mortality of several cancer types, including colorectal, stomach, esophageal, breast, lung, prostate and liver cancers.

Professor Hui Kam Man, an adjunct professor with the Cancer & Stem Cell Biology Programme in Duke-NUS Medical School, and Dr Xia Hongping, a researcher with National Cancer Centre Singapore (NCCS), reviewed such studies, and highlighted the emergence of aspirin in chemoprevention (preventing cancer) and as an adjuvant therapy in cancer.1

David Silver Photo

A discovery from Professor David Silver’s lab has been commercialised with the formation of Babynostics Pte Ltd, a newly launched Singapore-based company, which develops cutting-edge nutritional solutions to encourage healthy brain development for babies and children.

CTeD and Professor Silver have worked together to develop and commercialise this technology for the past few years. We spoke to Professor David Silver, Scientific Founder of Babynostics, to find out his perspective on working with CTeD and the formation of Babynostics.

1. Tell us more about what Babynostics does.

Babynostics has a pipeline to develop lysophospholipids, which we discovered to be essential for human brain development, as clinical nutrition therapies targeted to preterm, low birthweight infants who are at risk for developing neurological problems. In addition to developing therapies for this particular at risk population, Babynostics is exploring applications of lysophospholipid formulations for improving maternal and fetal nutrition. As the name implies, Babynostics is also developing a diagnostic platform to identify pregnant mothers at risk of delivering a preterm baby.

2. Tell us about your experience in working with CTeD and forming a company in Singapore.

Dengue fever, caused by the dengue virus, is a tropical disease transmitted by mosquitoes that threatens more than one third of the worldwide population, making it one of the most important arboviruses in the world. They have important economic consequences because of the burden to hospitals, work absenteeism and risk of death for severe symptomatic cases.

Dengue viruses are primarily transmitted from human-to-human by Aedes aegypti mosquitoes. While the mechanisms leading to dengue infection in humans have been defined, there is a lack of knowledge on how dengue viruses influence mosquito transmission and infection, or the genetic factors that affect virus replication in mosquitoes.

With this quest in mind, researchers at Duke-NUS Medical School’s Emerging Infectious Disease Programme led by Assistant Professor Julien Pompon and Professor Mariano A Garcia-Blanco set out to identify the viral determinants of transmission, as well as the mechanism by which dengue viruses harness evolution to cycle between the two hosts.

Gayatri SharmaWe speak to Dr Gayatri Sharma, Entrepreneur-in Residence (EiR) with CTeD, to find out how an EiR translates Duke-NUS inventions into commercial applications. 

1.       Tell us what you do as an EiR. 

 My primary role as an EiR is to create commercial value for the Intellectual Properties developed at Duke-NUS. Currently, I am working on developing a business plan around a Laminin platform technology developed at Professor Karl Tryggvason’s laboratory. Laminin-based technology enables us to grow cell types sustainably in large numbers by mimicking the environment of a human body. Some of these cell types include keratinocytes (skin cells), islets (insulin-producing cells) and cardiomyocytes (heart cells). This will address the huge market gap in cell production for therapeutic applications. We have seen great results in animal studies, and my job now is to chart the commercial path for this technology. 

 

Mosquitoes

Dengue and chikungunya are mosquito-borne diseases that are currently re-emerging as public health burdens worldwide. Annually, over 390 million people are infected with dengue, while chikungunya periodically emerges in highly populated areas. The primary vector for the two diseases is Aedes aegypti, a mosquito that thrives in domestic areas.

 Since there is no vaccine for these arboviruses, vector control remains the best way to control the incidence of these diseases. In the 1960s, the Singapore government started a vector control campaign in order to prevent the transmission of dengue by Aedes aegypti. Measures included mosquito and clinical surveillance, public health education, community participation, fines for allowing mosquito breeding, among others. While this campaign drastically reduced the number of households with Aedes mosquitoes and the incidence of dengue in Singapore until the 1990s, dengue epidemics have since increased in frequency, and chikungunya re-emerged in 2008.

 To better understand this paradoxical situation Principal Research Scientist Ian Mendenhall and Assistant Professor Julien Pompon from Duke-NUS Medical School (Duke-NUS) led research that investigated whether peridomestic areas, or areas near inhabited areas, could be the cause or source of these diseases.

Esther GanDr Esther Gan, recent Duke-NUS Medical School PhD graduate and speaker for her class shares with Microscope about her journey to Duke-NUS and her plans post-graduation.

How did you first learn about Duke-NUS?

I heard about Duke-NUS from one of my immunology professors during my undergraduate studies at the University of British Columbia.

I have always been interested in infectious diseases research and my experience in an influenza laboratory further piqued my interest in pursuing this avenue. Coincidentally, Dr Ninan Abraham had a collaborator, Dr Veronika von Messling, who had just moved to Duke-NUS to set up a lab and he highly recommended that I did a year of research with her. She was a veterinarian studying the pathogenesis of influenza in animal models. I ended up working for her for a year as a research assistant. It was amazing the amount of techniques that I learnt from her! We worked with mice, ferrets and monkeys all within a span of a year.

We see that you started your Duke-NUS journey as research assistant and not a PhD student. Why didn’t you jump right into the PhD programme and what finally made you decide to take the plunge?

I didn’t know how I would adjust to Singapore culture – the people and the research - after so many years abroad. My idea was to come, work for a year and assess if it would be a suitable place to do my PhD.  It was tough; I missed the nature, the four seasons, the ability to drive two hours and immediately hit a ski slope. But it wasn’t impossible; I did manage to adjust to life here!

That is the question. As the number of end-stage renal disease (ESRD) patients rises rapidly in Asia, the need for dialysis grows with it, along with a trend to start dialysis earlier in the management of ESRD. The situation in Singapore is similarly bleak. It is imperative to determine if the benefits of starting dialysis earlier is worth the high cost and inconvenience that accompanies it, especially when evidence supporting those benefits is limited and controversial.

Team Photo

The research team (L-R): Dr Feng Liang, Professor Tazeen Hasan Jafar, Dr John Carsen Allen.

Daryl Tan

The third year of research is a hallmark of the MD programme at Duke-NUS Medical School (Duke-NUS), which gives students a chance to flex their investigative muscles and figure out ways to treat diseases, improve patient care, better understand patients– or really do any kind of research that will improve people’s lives.

Daryl Tan really made the most of his third year at Duke-NUS. His biggest takeaway from the unique experience was that he learned to seize opportunities to work with the best mentors, to present his research in international conferences and to win prizes for his work.

During his second year elective in Women’s Anaesthesia in KK Women’s and Children’s Hospital (KKH), Daryl encountered brilliant, passionate and pro-teaching anaesthetists. For his third year, it was a natural choice for Daryl to do research at KKH under the mentorship of Associate Professor Sng Ban Leong, Director, KK Research Centre and Deputy Head and Senior Consultant, Department of Women’s Anaesthesia, KKH, and Professor Alex Sia, former Chairman Medical Board and Chief Executive Office and Senior Consultant, Department of Women’s Anaesthesia, KKH.

Cheung Yin BinAs part of an international research collaboration, Professor Cheung Yin Bun of the Centre for Quantitative Medicine (CQM) at Duke-NUS Medical School, developed a set of gestational weight gain (GWG) charts and published them in the prestigious American Journal of Clinical Nutrition [1]. Using prospectively collected weight measurements of pregnant women from 14 to 41 weeks of gestation and statistical methodology for longitudinal data analysis, the team developed not only a conventional, cross-sectional GWG chart but also longitudinal GWG charts, which takes prior weight status into account. That is, the (longitudinal) GWG chart for a woman is calibrated according to her weight in the previous visit, as opposed to using one chart for all women or one chart for a woman at all time.

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