Van B. Lu
Assistant Professor
PhD Pharmacology, University of Alberta
BSc Honours Pharmacology, University of Alberta
Post-Doctoral Experience National Institutes of Health (USA), University of Cambridge (UK)
Office: Medical Sciences Building, 229
t. 519.661.2111 x88176
f. 519.661.3827
e. vlu24@uwo.ca
Why Science (or Why Research)?
I always liked science as a kid and was excited about science projects since elementary school. Whether it was taking frog eggs home to watch them hatch or in high school chemistry labs, I enjoyed putting the knowledge we learned in class into real-life applications. My passion for science and research really developed at university in a lab where I had patched my first cell. I recorded the membrane activity from a single cell using a glass electrode and a microscope. I was able to see it fire an action potential and see it change its response as I applied different channel blockers. From this experience, I decided to pursue a career in research. In my Ph.D., I worked with Dr. Peter Smith, where I looked at the spinal cord and how pain signals are integrated and sent to the brain. During chronic pain disease states, there is a permanent change in spinal neurons, thus they continue sending pain signals even when there is no longer any tissue damage. I was able to identify the chemical mediator that produced the chronic changes in these neurons. At the NIH, I studied G-protein coupled receptors and the mechanism by which they modulate the activity of neurons. We also developed molecular tools to study ion channel modulation in neurons. In my second post-doc, I continued this line of inquiry in cells that released gut hormones, and how their ion channels are modulated by different nutrients and metabolites. I applied these methods to study hormone-releasing cells in the intestine, the enteroendocrine cells, to understand how nutrient-sensing G-protein coupled receptors can alter the excitability of these cells.
Research Goals:
The goal of my research is to understand how cells in the body sense its external environment and communicates this signal to the rest of the body to initiate an appropriate response. My current work focuses on gastrointestinal epithelial cells and how they sense nutrients and metabolites produced by gut bacteria. Basically, I am interested in how the cells lining the GI tract interact with the micro-organisms that reside in our gut. The gastrointestinal tract, particularly cells lining the intestinal epithelium, are the first point of contact between an organism and the food it eats or the bacteria that resides in their gut. But we know very little about the mechanisms by which these cells are able to sense these chemical stimuli. Understanding how the gastrointestinal tract responds to external stimuli can help us understand how dysfunction of this process may lead to disease such as during inflammatory bowel disease (IBD) or during chronic parasitic infection. Furthermore, we are developing the tools to allow us to interrogate how the gut microbiome can influence overall human health. Understanding how these cells work will help us understand the influence of the gut microbiome in human health.
My lab makes use of various techniques such as electrophysiology, molecular cloning, and calcium imaging. We also make use of modern 3D cell models called intestinal organoids. I have used mouse organoid models generated from transgenic mice lines that express reporter proteins within the enteroendocrine cell population. I have also generated a novel human organoid model labeling enteroendocrine cells via CRISPR/Cas9 technology to knock-in reporter genes into these cells. We have used these organoid models to elucidate the nutrient-signaling pathways within the enteroendocrine cell population. I have used these models to measure gut hormone release from enteroendocrine cells after exposure to nutrients and to measure intracellular calcium responses and membrane excitability, which are often altered following nutrient exposure We found that nutrient signaling pathways are able to recruit ion channels to alter the excitability of enteroendocrine cells and affect the release of gut hormones.
Specific Research Interests:
- Nutrient-sensing mechanisms in enteroendocrine cells
- Characterization of chemosensory mechanisms in intestinal Tuft cells
- Development of intestinal models to study intercellular communication within the intestine
Undergraduate Teaching:
PHYS 3120: Gastrointestinal physiology
PHYS/PHARM 4980E: Seminar and research project (undergraduate thesis supervisor)
SE 2200E: Seminar and research project (undergraduate thesis supervisor)
Most Rewarding Moments:
It is very rewarding to find solutions to problems, its like solving a good puzzle. In the lab, things do not always go the way that you would like them to, so it forces us to be flexible and creative. Helping others and working towards solving a common problem is very rewarding as well.
Advice to Students:
One piece of advice that I have for students is for them to not sell themselves short. You develop a lot of skills in science, such as how to review and evaluate literature, how to solve problems, and how to think critically. Even if you do not pursue a career in academia, you gain a lot of these valuable transferrable skills. These skills are incredible assets in many different jobs and will really help you make informed decisions in your life.
Interests Outside of Academia:
I am a huge fan of baking, as well as watching movies in my free time!
Awards and Recognitions:
Year Name of Award
2021 Gairdner Foundation Early Career Investigator Award
2019 Best Oral Presentation at the EASD Incretin Study Group Meeting
2017 Early Career Grant from the Society for Endocrinology
Highlighted Publications:
VB Lu, FM Gribble and F Reimann. Nutrient-induced cellular mechanisms of gut hormone secretion. Nutrients, 2021 Mar 9; 13(3): 883. doi: 10.3390/nu13030883. [PMID: 33803183]
DA Goldspink*, VB Lu*, EL Miedzybrodzka*, CA Smith, RE Foreman, LJ Billing, RG Kay, F Reimann and FM Gribble. Labelling and characterization of human GLP-1 secreting L-cells in primary ileal organoid culture. Cell Reports, 2020 Jun 30; 31(13):107833. (*co-first authors). [PMID: 32610134]
VB Lu, J Rievaj, EA O’Flaherty, CA Smith, R Pais, LA Pattison, G Tolhurst, AB Leiter, DC Bulmer, FM Gribble and F Reimann. Adenosine triphosphate is co-secreted with glucagon-like peptide-1 to modulate intestinal enterocytes and afferent neurons. Nature Communications, 2019; 10(1): 1029. [PMID: 30833673]
VB Lu, FM Gribble and F Reimann. Free-fatty acid receptors in enteroendocrine cells. Endocrinology, 2018; 159(7): 2826-2835. [PMID: 29688303]
DA Goldspink*, VB Lu*, LJ Billing, P Larraufie, G Tolhurst, FM Gribble and F Reimann. Mechanistic insights into the detection of free fatty and bile acids by ileal glucagon-like peptide-1 secreting cells. Molecular Metabolism, 2018; 7:90-101. (*co-first authors). [PMID: 29167062]
