1. Can you please briefly summarize the paper? 

Weight loss predicts faster disease progression in amyotrophic lateral sclerosis (ALS). Prior studies have focused on supplementing calories without identifying key macronutrients. In the current study, Dr. Ikjae Lee, in collaboration with Dr. Hiroshi Mitsumoto and colleagues from Columbia and the University of Kentucky, analyzed dietary patterns in the ALS COSMOS cohort to examine whether a specific macronutrient intake is associated with functional decline and survival. Published in the?Annals of Neurology, we found that diets with a higher glycemic index (GI) and glycemic load (GL) are associated with slower functional decline and longer survival. GI and GL are classifications of dietary carbohydrates based on postprandial glycemic response, whereby a higher GI diet leads to a higher and quicker rise of blood glucose. Our findings are counterintuitive since high GI and GL diets may contribute to metabolic syndrome and cardiovascular diseases and are largely discouraged in the general population. Nonetheless, the results are in line with prior studies demonstrating a protective effect of cardiovascular risk factors, such as obesity and diabetes mellitus, in ALS occurrence.

2. Can you please tell us the main difficulties you had in the laboratory work and how you overcame them?

My research focus is to translate laboratory research findings into improvement in ALS patient care. While studying in-vitro and in-vivo disease models in the basic science laboratory is critical for elucidating disease mechanisms, substantial efforts are needed to translate such findings to successful development of therapeutics. With my background as an experienced neuromuscular and ALS specialist, I can leverage clinical cohorts of ALS patients for prospective studies and clinical trials. Working at Columbia University provides me with access to various resources including patient population, versatile research team, network of collaborators, research equipment, and infrastructure. I recently received a K23 career development award from the National Institutes of Health (NIH). This has provided me with protected research time which is essential in keeping my focus in the research area in which I am interested.

3. Please introduce your laboratory, university or organization to bio-researchers in Korea.

Eleanor and Lou Gehrig ALS Center at Columbia University is one of the largest ALS centers in the United States (US) serving over 400 individuals with ALS and related motor neuron disease (MND) patients annually. A multidisciplinary team of five ALS physicians and associated healthcare professionals and support staffs offer compassionate care to ALS/MND patients and families and provide the resources necessary to meet the evolving challenges of living with MND. Research activities, including genome analysis, observational studies, and clinical trials, are integrated into the ALS Center clinics to give individuals the opportunity to participate in the fight against ALS/MND. Among many research projects, we can highlight two studies. First, international phase 2-3 trial of ION363, an antisense oligonucleotide targeting FUS gene. It is designed to specifically bind to and degrade RNA arising from this gene, thereby reducing the level of FUS protein. Mutations in the gene lead to abnormal FUS protein which mis-localizes from the nucleus to the cytoplasm, forming toxic clumps. Evidence suggests that the abnormal FUS has a toxic gain-of-function in ALS, meaning that it gains extra functions that are toxic to the cells. This is thought to be the driving force behind the disease in FUS-ALS. Consequently, suppressing?FUS?gene expression, which would reduce the amount of abnormal FUS protein, may help alleviate toxicity and reduce neuronal damage.?Second, the ALS Families Project is an ongoing prospective study that provides genetic counseling, testing, and follow-up monitoring of ALS symptom onset in at-risk individuals who are related to an ALS patient who harbors an ALS-causing pathogenic variant(s). During my K award period, I aim to study the alteration of metabolism in presymptomatic individuals harboring C9orf72 and whether these changes might influence the probability or onset timing of ALS symptoms. Ultimately, I am interested in developing therapeutic strategies to prevent ALS onset in this high-risk population.

4. Please tell us your experiences and your thoughts related to research activities abroad.

In the United States, there are many different pathways and funding for researchers at various stages. One example is the Mentored Patient-Oriented Research Career Development Award program (K23) which provides support for an intensive, mentored research career development experience for individuals with a clinical doctoral degree who have committed to patient-oriented research. Those who graduated from medical school and completed residency/fellowship training are competent in taking care of patients. One might have various degrees of experience in research, but this is often not sufficient to function as an independent investigator to take on major research questions or obtain substantial research funding. K award provides time and resources for young investigators to learn deficient skills from mentors to subsequently establish their research niche and apply for independent research grants. This is only one example of many other grant mechanisms that can be utilized by researchers in both clinical and basic science fields. There are countless different grant opportunities from various sources such as government, foundations, industry, and institutions. I believe that research opportunities are given to both US citizens and non-citizens if the candidate has passion and capability for research.

5. Can you provide some advice for younger scientists who have plans to study abroad?

I am still in the early stages of my career, especially in research. I have limited research experience in Korea, which makes it difficult for me to recommend for or against studying abroad. I believe that opportunities are all around us, some better than others, regardless of where you are. I find it critically important to find your research interest and perseverate on the subject while keeping your attention to funding opportunities that will help you achieve your goals. First and foremost, research should be enjoyable. It shouldn’t be an obligation or something you are told to do. Find a research question or subject that you are so eager to find the answer to. Question that might stop you from sleeping or wake you up in the middle of your dream. Practice your research methods whether that is a scientific experiment or data analysis. Be the best and most knowledgeable person for what you do among your peers in your lab, institution, and even the nation. Write manuscripts and research proposals and learn how to convince other people of what you found and the value of your research. Find people who share your passion and learn from them.

6. Future plan?

My long-term goal is to develop novel treatments to stop the progression of ALS and prevent the onset of the disease in high-risk populations who carry pathogenic variants. This has proven to be extremely difficult not only in ALS but also in other neurodegenerative diseases like Alzheimer's and Parkinson’s disease. In the short-term, I aim to successfully complete my current projects and prepare myself for independent research grant application in the next 5 years.

7. Do you have anything else that you would like to tell Korean scientists and students?

I want to emphasize the basics: find your passion; persevere; ask for help and help others in return.