Dr. David Knapp shares his work examining how growth factors affect the survival, proliferation, and maintenance of cells of the cord blood HSC compartment

A Hematopoiesis Researcher's Goals, Challenges, and Needs for Superpowers

David Knapp, Ph.D., Postdoctoral Fellow, Dr. Tudor Fulga’s Lab, University of Oxford
David Knapp, PhD

Interviewed by Amanda Fentiman, RND at STEMCELL Technologies

I met Dr. David Knapp when he was simply “David Knapp” (the inclusion of his surname was important to distinguish him from other Davids in the building), as we were both developing our expertise in hematopoietic stem cell biology - with projects that involved long hours behind instruments in our building’s flow cytometry core. David was a PhD student in Dr. Connie Eaves’ lab, while I was an MSc student in Dr. Aly Karsan’s lab, both at the Terry Fox Laboratory located within the BC Cancer Research Centre (BCCRC) in Vancouver.

In December 2015, David completed his PhD in the Experimental Medicine program at the University of British Columbia, after successfully defending his PhD thesis on hematopoietic stem cell identity and behaviour. Moving to expand his horizons to synthetic biology, in the week following this interview, David moved to the United Kingdom and is currently working as a postdoctoral fellow in Dr. Tudor Fulga’s lab at the University of Oxford. Like any good grad student and scientist, David is continuing to work to publish three papers based on his doctoral work, with Dr. Eaves.

The Expert

Amanda Fentiman: Superheroes always have an origin story; scientists are no different - when did you first know you wanted to become a scientist, basically - what sparked your love of science?

David Knapp: I don’t remember this but apparently when I was 4 years old I told my parents that I wanted to be a scientist. I think I actually wanted to be a wizard... but this was the next best thing to be done in real life, so I settled for “scientist”.

AF: Sounds like a better choice, being a scientist involves long hours, but I can’t even imagine how long it would take to become a successful wizard. In addition to dabbling in wizardry, what are some of your non-lab-based interests?

DK: Martial arts is a big one. I’m an instructor at Tong Moo Do (TMD) Martial Arts in Richmond, BC, and I’m there many days a week. It’s a good and necessary balance to the lab. If you have a day where your experiments have gone poorly - it’s good to be able to go hit things and get out your frustrations.

AF: I think most of of us have had days like that in the lab, I know I certainly have! Can you think of something that could have made your experiments easier, perhaps even a superpower that would’ve been useful for you, but may been seen as useless by non-scientists?

DK: Instant centrifugation. Just hold the tube and you’ve got your pellet!

AF: That would be amazing! Although, hopefully it wouldn’t be automatic, sometimes you need those single cell suspensions for staining or plating. If you couldn’t have instant centrifugation - what piece of non-existent technology could’ve helped you finish your PhD in half the time?

DK: Easy - a molecular assay for stem cell function - that would be the single greatest advance in experimental hematology in a long time. It sounds boring; it’s “just an assay” but if it’s faster than a year long in vivo assay - it would be very well received.

The Experiments

AF: Now that we know a bit about the person behind the scientist - back to the science. What are your current research goals in Dr. Eaves’ lab?

DK: My current research is divided into two sections that will hopefully become three papers. The first main focus is looking within the human cord blood HSC compartment and seeing how these cells respond to growth factors with respect to survival, proliferation and stem cell-state maintenance, including how those three programs are related, e.g. can you activate one of them without activating the others?

The other section involves looking at the entire hematopoietic hierarchy to map functional measurements with molecular readouts for different cell types, allowing us to place this information in the classical hematopoietic hierarchy. For example, is this set of parameters defining only one cell type or are there multiple molecular subtypes? This way we can build a molecular hierarchy within different progenitor cell subtypes.

AF: Each field and specification has its perks in terms of the cool assays you get to do, the things you get to talk about, or the impact of your research. What is the best thing about studying hematopoietic stem cells?

DK: Single cell analysis - it always gives you massive datasets to play with, which is the best and worst thing to have data on millions of cells with tens to hundreds of parameters on each. You are never bored as there’s always another question to ask the data. This includes technologies like CyTOF , and Drop-seq; there are even some low cell number epigenetic methods being developed. Eventually we will have to change how we define different cell types as the hematopoietic hierarchy will break down and become more of a continuum.

The Expertise

AF: Of course your research doesn’t exist in a vacuum, let’s talk about hematopoietic research in general. What are the major challenges in solving the ‘big questions’ in your field, whether it’s technology or biological limitations?

DK: Lack of a clear readout. It’s very challenging to give definitive/fast readout about a cell’s identity and potential. Even definitive assays and their readouts [like in vivo experiments] may change with using different mouse models, or there may be an interaction that is required between cells. Some cells do readout at the single cell level, but this is often a smaller population than is identified in a limiting dilution assay (LDA). The vagaries of mouse models could be answered with good molecular tools but these would have to be validated with mouse models and ultimately in clinical trials.

AF: Where is research in your field headed or where would you like to see it go?

DK: Ultimately the goal would be that you could grow human HSCs in infinite amounts, and have vats frozen down for patients as necessary and on-demand for any indication or to allow gene therapy for patients with no other treatment options.

AF: Now that you’ve defended your thesis, what are your plans from here?

DK: I’m going to Oxford for a post-doctoral position related to synthetic biology. We are getting to the point where we can’t make any broad generalizations about cell types and now instead I think we are moving towards engineering, like figuring out what you want the cell to do, and how to make the cell do it. This is my next adventure!

AF: Congratulations! So, for the trainees out there reading, how did you get this postdoc?

DK: One night, I had just gotten home from a friend’s wedding down in the United States, and I remembered there was a talk happening at the BCCRC so I hopped on my motorcycle and made it there in time. It was a great talk and afterwards I started talking to the presenter, Dr. Thomas Milne (the presenter), and explained to him what I was interested in pursuing next. He introduced me to Dr. Fulga, I talked to him, and now I’m flying to Oxford next week!

AF: Wow, that is quite the fluke! Just goes to show there is no book or set of rules to follow on these kinds of things. It’s all about being around at the right time and making sure you are talking to people.

DK: Even coming to my PhD lab was a fluke. I was interviewing with another lab and they said why don’t you go interview with Dr. Eaves? And it worked out!

AF: It certainly did! Thank you so much for speaking with us today David, and good luck in your next adventures!

This interview has been condensed and edited.

Amanda Fentiman is a member of the Hematopoietic team in RND at STEMCELL Technologies in Vancouver, Canada.

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