Dr. Camila Esguerra heads Oslo’s Centre for Molecular Medicine Norway. (Photo: Oda Hveem)

 

Updated: January 25, 2020, 11:40 A.M.

Filipina scientist is one of world’s leading researcher on epilepsy using zebra fish

By Teodoro Alcuitas

A Filipina scientist is leading one of the world’s leading centre on epilepsy and drug research using an alternative model. 

While scientists use a range of model organisms to understand human biology, from basic single-celled yeast to more complex animals such as flies and mice, Dr Camila Vicencio Esguerra at the University of Oslo uses an alternative model: the zebrafish.

Dr. Esguerra heads the Centre for Molecular Medicine Norway (NCMM) and also has her own research group based at the university. The  group use zebrafish to study the human central nervous system, meaning the brain and spinal cord, and related diseases such as epilepsy, schizophrenia, and autism.

Born and raised in White Plains, New York, she is the eldest of two daughters of Carlos and Carolina Esguerra. She had her early schooling in Luther Lee Elementary public school in Demarest, NJ where the family lived before returning to the Philippines in 1979. 

Dr. Esguerra (2nd from left) with sister Ivilisse, mother Carolina and father Carlos at the 2007 during her defense of her doctoral thesis at the Katholieke Universiteit Leuven (KUL), Leuven, Flanders, Belgium. (Photo provided)

She continued her primary education in the Philippines at Jose Abad Santos Memorial School (JASMS) in Quezon City where she graduated valedictorian. She then attended the Philippine Science High School (PSHS) and learned to play the electronic organ under Mrs. Carmencita Arambulo. After graduation she was accepted at Wellesley College near Boston. Her studies at Wellesley prompted the family to move back to United States in 1986.

Educational  and teaching trajectory 

Education:

02/2003-07/2007: Doctor of Medical Sciences (PhD), University of Leuven, Belgium

09/1992-08/1994: Master of Philosophy (MPhil) (Developmental Genetics)

  • Max Planck Institute for Developmental Biology, Tübingen, Germany
  • MRC National Institute for Medical Research, London, United Kingdom
  • Open University, Milton Keynes, United Kingdom

09/1986-06/1990: Bachelor of Arts in Biological Sciences (BA), Wellesley College, Wellesley, MA, USA

Teaching:

2015 – present:

Lecturer, School of Pharmacy, University of Oslo, Norway; Organic Chemically-Based Drug Design

01/2004 – 11/2014:

Lecturer, Biomedical Sciences Group, University of Leuven, Belgium; Principles of Genetics, Model Systems in Research, Laboratory Animal Science

Research:

University of Leuven, Leuven, Belgium:

10/2008 – 11/2014:

  • Senior Scientist and Industrial Research Fellow, Laboratory for Molecular Biodiscovery, Department of Pharmaceutical Sciences and Pharmacology
  • Founder and Manager, Chemical Genetics Initiative @ KU Leuven
  • Project Coordinator, PharmaSea (EU FP7 Project, 2012-2014)

08/2006 – 01/2008:

  • Postdoctoral fellow, Laboratory of Catherine Verfaillie, Interdepartmental Stem Cell Institute

08/2006 – 01/2008:

  • Postdoctoral fellow, Laboratory of Frank Luyten, Laboratory for Skeletal Development and Joints, Department of Musculoskeletal Sciences

02/2003 – 04/2006:

  • Senior Scientist and Doctoral Candidate, Laboratory of Desiré Collen, Molecular Cardiovascular Medicine Group, Faculty of Medical Sciences

Continuing her educational trajectory, she cross- enrolled at MIT and Harvard for additional science courses. While doing her senior research/thesis at Harvard University, she was recommended by her professor to the Whitehead Research Institute at MIT where she worked under Richard Mulligan, the promising young scientist who who developed the technique of transferring a gene from one cell to another using retrovirus.

After a few years stint at Whitehead Institute, she and her German-American husband who she at MIT, moved toTübingen University in Germany where both worked at the Max Planck Institute for Biology Research. They trained in the use of the zebrafish for molecular biology research under Dr. Christiane Nüslein-Volhard, 1995 Nobel Prize winner in Medicine.

After Tübingen University, the couple studied at the Katholieke Universiteit Leuven in Belgium where Esguerra obtained her doctorate in Medical Sciences in 2007 and where she co-led a research group using zebrafish. She was recruited by Oslo University in late 2014 to start a zebrafish research program in Norway.

“The greatest advantage of zebrafish is the fact that they are transparent during the first weeks of development”, explains Dr Esguerra in an interview with Oslo University.

https://www.med.uio.no/ncmm/english/news-and-events/profiles/researcher-profile-dr-camila-esguerra-using-zebraf.html

“This means researchers can easily view internal organs such as the brain, and monitor its activity using non-invasive imaging in live, freely-moving animals. This makes it possible to monitor neural activity patterns associated with specific behaviors in the fish; for example, during prey capture or even when they are having convulsions as a result of seizures.”

Studying zebrafish then, helps researchers to understand human brain function, health and disease.

“Zebrafish and humans are actually quite similar when it comes to genetics and neurology”, says Esguerra.

Indeed, you may be surprised by how much zebrafish and humans have in common. In terms of physiology, zebrafish have all of the same organs as humans, with the exception of lungs and a uterus. Genetically, scientists now know that around 70% of human genes have an equivalent in zebrafish. Furthermore, if you compare genes linked to disease, the degree of overlap is even higher. For example, 88% of all human schizophrenia risk genes have equivalent copies in zebrafish.

Adding and removing genes to understand epilepsy

Dr Esguerra has been involved in a range of studies using zebrafish to investigate neurological diseases.

“Prior to starting my group in Oslo, I co-led a study that used zebrafish to identify a new gene involved in fever-induced seizure susceptibility, which affects 2-4 per cent of all children and is also linked to epilepsy. When this gene is switched on it produces a protein called ‘Syntaxin 1B’, and forms part of a larger multi-protein complex essential for the release of neurotransmitters – the chemical signals that nerve cells use to communicate with one another. We found that deleting (knocking-out) this gene caused the same symptoms in fish as seen in humans, with spontaneous seizures that increased in severity when we simulated fever-like conditions”, she says.

This indicated that faulty Syntaxin 1B might be involved in inducing seizures in humans – an idea that was supported by other factors. Dr Esguerra continues:

“The zebrafish and human Syntaxin 1B genes are almost identical in sequence. We were able to cure the Syntaxin 1B knockout zebrafish of their seizures by switching on production of human Syntaxin 1B in their cells. Conversely, when we introduced the Syntaxin 1B gene from one of our seizure patients into the knockout fish, this could not rescue the fever-sensitive epilepsy symptoms”.

Proud father: Carlos Esguerra took early retirement from his computer business and is an accomplished landscape and architectural photographer. (Photo: Carlos L. Esguerra Photography)

These findings strongly indicated that the patient’s Syntaxin 1B was faulty and causing disease symptoms. Therefore, it may be that Syntaxin 1B is a good target for therapy to treat these seizures.

“Here in Oslo, we are building upon this work by using zebrafish to investigate a range of other genes linked to causing epilepsy in humans. This will help us to understand the relative involvement of these genes in different aspects of disease – for example, do mutations in certain genes make an individual more susceptible to epilepsy, or perhaps make certain symptoms more severe. In parallel, together with collaborators at the University of Luxembourg, we are using fish epilepsy models to test whether certain genes make people resistant to specific types of seizures. Some of our new data indicates that we may be able to identify genes that protect individuals from seizures.”

Assessing drugs to treat a rare infant syndrome

Another approach utilized by the Esguerra group involves introducing known disease-causing patient mutations into zebrafish genes to model different human disorders, then screening these fish using a range of drugs. Any drugs that appear to relieve disease symptoms in the fish models could therefore provide useful tools for treating patients.

In a recent study, the Esguerra group investigated the potential of certain drugs to treat Dravet syndrome, a very severe and devastating type of epilepsy occurring in infants and children.

“We were able to show that several drugs work just as well in our fish model as they do in human patients participating in clinical trials. One drug, called fenfluramine, is pending FDA approval and we have shown that it has ‘disease modifying’ activity in our fish models. In other words, it not only significantly reduces the number of seizures but, when given early enough during brain development, it corrects the brain defects associated with seizures.”

Such studies are difficult to assess in human patients, as these types of epilepsies are rare, meaning it is difficult to recruit the numbers of patients required. Also, data must be collected over very long periods of time – often several years or longer. Of course, patient-based safety and efficacy studies should nevertheless be carried out at later stages. Dr Esguerra hopes that her group’s findings in zebrafish will help guide future human patient studies.

Using zebrafish to study cancer

Zebrafish are not only a useful tool for the neurology research field.

“The small size of zebrafish embryos and larvae make them a great tool for large-scale screening approaches commonly used to answer a range of fundamental biological questions”, says Esguerra.

For example, using just a few small culture plates it is possible to simultaneously test hundreds of different drugs for their overall toxicity and/or effects on specific organs.

“As an alternative to testing drugs, we can also screen many different genetic mutations to assess which genes are involved in the growth, development, health and disease of the zebrafish. Again, many studies have shown that genes identified in this manner play similarly important roles in humans”, she says.

This versatility means zebrafish are nowadays used by researchers from across the world to study many different human diseases including muscular dystrophy, deafness, Parkinson’s disease and even type 1 diabetes.

Zebrafish can also be used to model one of the biggest human killers – cancer. One example comes from so-called ‘patient-derived xenograft’ (PDX) zebrafish models. Here, zebrafish are injected with human cancer cells, which form tumors within the fish. Researchers are then able to see how fully formed tumors respond to various treatments administered to the zebrafish, for instance new drug leads for cancer therapy. Compared to experiments performed in a cell culture dish, PDX models enable scientists to study cancer cells in an environment that is more similar to the ‘real life’ tissues and organs in which they reside in human patients.

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The Esguerra Research group, always thinking about zebrafish.

Further details:

In addition to running her own research group, Dr Esguerra also heads the zebrafish core facility at NCMM. This facility enables other researchers without the necessary expertise to perform experiments using zebrafish, thereby gaining important biological insight into their research question using living animals. Learn more about the facility on the NCMM website.

More information about the Esguerra group and their research aims is available on the NCMM website.