Hypertension 2019 Early Career Oral Award Winners

Hypertension 2019 Early Career Oral Award Winners

September 11, 2019 1 By Jose Scott


(gentle music) – Hello, I’m Dr. Francine
Marques from Monash University, and I’m here with the two winners from Hypertension Council Awards from the basic and clinical science. So Dr. Giacomo Rossitto and Karen Clark. Welcome. – Thank you very much. – Giacomo, can you tell me a
little bit about your study? – Sure, so what I try to
present as part of my work on new concepts related
to household associated with cardiovascular
disease and in particular there’s some novel concepts
which would suggest how salt can induce cardiovascular
disease independent of blood pressure by changes in metabolism. That’s what we explored in
a quite unique population of patients, very carefully
characterized group of patients in the University of Padua,
which were our collaborators. This cohort gave us a chance to show how our kidneys are able to
handle in different way salt and water upon high salt intake which is a condition which
would otherwise lead to some loss of fluid and fluid imbalance to a point that the more salt you eat the more your kidneys are able to deal with these salt preserved water but obviously spend energy to this extent. And this in the end
would result in changes in metabolism a sort of catabolic state which would induce a loss
of important proteins and overall this shift which
can be in the long term and overall this shift which
can be in the long term detrimental symptoms
of cardiovascular risk. – Okay, amazing. So can you tell me in one sentence what is your take home message? – My take home message is in a sense the more salt you eat,
the more you would eat. – Okay, yep, amazing, yeah. And Karen, you’re doing some studies looking into generic model
that lie on rat, is that right? – Mmm-hm, yep. – Can you tell me a little bit about it? – Sure, so our lab’s
mission is using genetics and genetic tools to discover new ways and genetic tools to discover new ways to understand hypertension
and obesity, and you know, to understand hypertension
and obesity, and you know, dyslipidemia, anything that’s involved in the metabolic syndrome. And the really cool talk
we had on the first day And the really cool talk
we had on the first day of twelve hundred new steps
they found and validated is really interesting
but the thing is I agree with one speaker who said that that’s way too many to look at. And that’s for a couple of reasons. A, nobody’s going to have
all twelve hundred risks, sorry, that would just be
astronomically horrible and they would have the
worst luck of all time. But the thing that’s
important is like finding things that are in novel pathways
you may not have expected. You know a lot of people say, whoa we didn’t expect this gene ’cause it wasn’t a renin or something. And there’s a lot of genetic
mechanisms that contribute in ways that people don’t expect. So we had a rat model where
these two rats only have maybe a thousand maybe a thousand none’s anonymous variants but it’s like a difference between a runway model and a sumo wrestler in terms of phenotypic diversity. So clearly there’s not a lot going on that’s different there genetically, and yet phenotypically
they’re amazingly diverse. So we decided that that was
a really excellent model to untangle the genetic causes of disease. And so we had classical QTO mapping, we did EQTO mapping, and the areas that we focused on were important in both studies. And then within that area, there’s not a lot of variation
that we had to go look at because these two strains are so similar. And in that area that was interesting we found my candidate gene, which is, sorry it’s got a horrible name, C17H6 or 52, C17H6 or 52, I promise I will name it properly when I have a mechanism,
but it was involved in, when I have a mechanism,
but it was involved in, it was differentially regulated
between the two strands, the fat one and the skinny one. And it was, it seemed really
like a good candidate. So we knocked it out and the, So we knocked it out and the, so my favorite part about this
from a geneticist perspective is that we knocked it out and
we allowed cellular repair to just repair it in
whatever way it would. So the Cas9 enzyme did a
double strand break and then So the Cas9 enzyme did a
double strand break and then the cells repaired one way
with a five base pair deletion and then another way with
a 10 base pair insertion. So same exact site targeted, So same exact site targeted, and two different repair mechanisms and yet they have no common phenotypes. So that really tells you that it’s a lot more complex in we feared but that’s still kind of exciting too because you wouldn’t want
to study a complex disease as a geneticist if you
were afraid of complexity. So, that’s basically it. – Beautiful, so what is
your take home message? – Rats, it’s complex. (laughing) – And humans as well. – And humans as well. – Congratulations to both of you. – [Giacomo & Karen] Thank you. – You did amazingly well. And you should be really
really proud of the result. – Thank you very much. – Good job. – Thank you. (gentle music)