June 16, 2025 • 19 mins
Each year, more than 800,000 Americans suffer a heart attack and many of those who survive are left with irreversible scarring and the slow progression towards heart failure. In this episode, Edward Thorp, PhD, explains how his team is exploring immune cells that influence the heart’s ability to heal after such injuries. In Thorp’s lab, they are uncovering fundamental molecular mechanisms by which the immune system regulates wound repair, reduces inflammation and regenerates tissue.
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(00:10):
This is Breakthroughs, a podcastfrom Northwestern University
Feinberg School of Medicine.
I'm Erin Spain, host of the show.
Each year, more than 800,000 Americanssuffer a heart attack, and many
of those who survive are left withirreversible scarring, and the slow
progression towards heart failure.
(00:31):
Today's guest, Edward Thorp.
Exploring how immune cellsinfluence the heart's ability
to heal after such injuries.
Uncovering fundamental molecularmechanisms by which the immune system
regulates wound repair, inflammationresolution, and tissue regeneration.
He is the Frederick Robert Zeit Professorof Pathology here at Northwestern,
(00:51):
and I am happy to have him on the showto talk about his research that is
helping to pave the way for the nextgeneration of cardiovascular therapies.
Welcome.
Hi, Erin.
Thank you so much for inviting me.
Very happy to be here.
So let's start off by telling me aboutthe focus of your lab and how you began
studying immune cells and inflammationin the context of heart disease.
(01:14):
Yeah, happy to Aaron.
Thanks for the, the question.
My fundamental basic training isin, microbiology and immunology,
actually right here in Chicago.
My lab study is really the fundamentalbiology of immune cells and their role
in inflammation and tissue injury.
Now, typically when people hearabout immunity, they first think
(01:34):
about, you know, immunity againstinfection, bugs, viruses, and COVID.
But it's really important to know that.
your immune system performs other keyfunctions besides combating infection.
For example, your immune cells oryour white blood cells or leukocytes
are critical for tissue repair afteryou scrape your knee and for example,
and, and tissue repair declines,unfortunately, as we age, and we can
(01:56):
all see this, uh, as we get older.
So a major focus of the laboratory is touncover how immune cells regulate tissue
repair and tissue regeneration now.
in addition to our, our basicscience research, we also perform,
clinically relevant, research.
And our clinical, uh, research focusis inflammation during cardiovascular
disease and heart failure.
(02:17):
So, for example, hundreds of thousandsof people each year suffer heart
attacks or myocardial infarctions,and after mi. Or a heart attack
your immune cells or leukocytes arecritical for clearing out the injury
and orchestrating a scarring response.
The trick is that, uh, your leukocytesdon't do a very good job, and this
is because, uh, your immune systemhas evolved mostly to protect us
(02:40):
during our childbearing years.
So we're living much longer now, and soour leukocytes are being exposed to new
types of disease, including heart failure.
And so this is actually a bigopportunity to translate our
fundamental science, uh, into therapy.
And so we're fortunate to do researchhere at Feinberg School of Medicine,
where we work very closely withphysicians and physician scientists
(03:03):
to investigate and translate andimplement therapies, , for disease.
Heart failure with preservedejection fraction or HFpEF.
This is a condition that accounts formore than half of heart failure in the us.
Can you tell me about this condition?
What makes it so challengingto treat and how you've, paired
with other investigators at themedical school , to look into this?
(03:26):
Yeah, good question.
And, and as you mentioned, um, Heartfailure with preserved ejection
fraction or HFpEF, is really themost prevalent type of heart failure.
in fact, sometimes it's called,huff puff because, uh, it.
Causes a shortness of breathand, and exercise intolerance.
And, and so look, I'm not a physicianand HFpEF is a, a technical term, but
(03:47):
what it really does mean for the layaudience is that the heart is fine in
its pumping capacity, but it can't fill.
Properly.
And so the results, uh, means thatyou have reduced, blood supply to
the rest of your body and some of theconditions that are associated with that.
So, despite the prevalence and theimportance of this syndrome there really
are very limited, uh, treatment options.
(04:08):
And so research into thisarea is very ----important.
Yes, because as you said earlier,this really is a disease of aging and
people are living longer now, and thisis something that a lot of people at
Northwestern and beyond are focused on.
HFpEF is definitely a disease of aging, asyou mentioned, and aging is a important,
uh, risk factor for its pathogenesis.
(04:29):
Other risk factors include obesity,metabolic syndrome and hypertension.
And so there is a large need inorder to understand and treat
this very heterogeneous syndrome.
And so, kind of delving a littlebit deeper into the focus of
our, our research and how thatinterfaces with this syndrome.
We've known for years that,HFpEF is associated with, , a
(04:50):
generalized inflammatory syndrome,inflammatory activation in the body.
What we didn't know.
Uh, however precisely is thecontribution and source of this
inflammation during disease.
And so this was a question of Dr.Mallory Philip in the laboratory
when she was a graduate student.
And this was also a collaboration withDr. Sanjeev Shah here at Northwestern,
(05:11):
who's an international expert inheart failure and heart failure
with preserved ejection fraction.
Mallory also worked closely withanother physician scientist, uh, Dr.
Matt Feinstein, who's also an expertin cardiovascular inflammation.
so in this new study published inCirculation, your team looked at how
fatty acid metabolism and immune cellscan drive blood stem cell activation
(05:33):
and heart failure , or HFpEF.
Tell me about this study and the results.
What did you find?
Absolutely.
So, Mallory really was the,the key driver of this study.
And what she discovered was thatpatients with HFpEF had a very unique
immune signature, uh, in their blood.
Uh, specifically, uh, patientshad an elevated immune stem cell
(05:56):
or progenitor cell signature.
And what this means isthat patients actually had.
A very early stage activationof their immune compartment.
Now, property of immune stemcells is that they can generate
many more progeny immune cells.
And so in this context it's reallyimportant to point out that,
immune activation to a certainextent is good and protective.
(06:16):
But if you have too much inflammation,for example, activation of these stem
cells, this can actually do harm.
So, for example, too many leukocytesthat infiltrate the heart can lead to,
unnecessary scarring response, which canimpair the ability of the heart to relax.
I will add, you know, a little bit of asa basic science, uh, test a little bit of
the underlying molecular mechanism that.
Mallory discovered in getting toyour point about the fatty acids.
(06:38):
so in addition to discovering thisfundamental,, insight and into
increased, stem cells during thiscondition, she also studied how the
stem cells were being activated.
And it's really important to pointout that these fundamental questions
are really important in revealingnew molecular therapeutic targets.
So a risk factor for Hef.
Path is obesity or high body massindex, as well as disturbed metabolism
(07:01):
and aging, as we mentioned earlier on.
And typically we think about metabolismas contributing to energy demands, right?
However, how metabolites canalso regulate immune cell.
Function that is separate fromjust energy is really kind of a
cutting edge area of research thatwe don't know too much about now.
And so what Mallory discovered inthis context with that increased fat
(07:22):
and lipids, uh, in these patientswe're capable of reprogramming the
genetic architecture or the geneexpression, in these immune cells to
activate stem cell growth factors.
so to test the therapeutic principle ofher findings, she employed an experimental
model I. Of this disease to block the fatuptake specifically in the immune cells.
(07:44):
And really impressively, she wasable to improve cardiac function
by this immune targeting approach.
Now this is promising, uh, becauseit's much easier intractable to target
your immune cells in the blood ratherthan invasively target the heart.
So what's next with this project?
You've published theseresults in animal models.
Where, what, where do we go next?
Yeah, absolutely., That's, youknow, the million dollar question.
(08:07):
And I think to translate these findingswe would really like to leverage some of
the expertise that's here at Feinberg andalso in Evanston and the really talented
bioengineers who are able to engineerplatforms and molecular targeting to.
Really try to, uh, block this, uh, immunometabolic pathway that's wreaking so much
havoc on immune cells and, and the heart.
(08:29):
And so we've been fortunate to,initiate collaborations with a Dr. Uh,
Lisa Ti and Dr. Pang Zang Pang beingat Feinberg and Lisa up in Evanston.
And so I really.
Think this is the next phaseof the translational work.
But I also, you know, really alsowanna stress as a, as a basic scientist
that we also are informed for clinicalapproaches with through the basic science.
(08:52):
And so really, uh, a main.
Another parallel main focus of thelaboratory is this, again, intersection
again, a metabolism and immune function.
And I won't get into the weedsof the, metabolic pathways, but
we've also been fortunate tocollaborate with investigators here
at Northwestern, including, uh,Nadel and Sam Weinberg for this.
And so really a lot that wedon't know about how metabolism
(09:12):
and metabolites regulate immunecells and their function that's
independent of their energy functions.
And this is particularly importantin cardiovascular disease where
these diseases are often accompaniedby a number of metabolic syndromes.
So this paper is part of anAmerican Heart Association
initiative investigating the role ofinflammation in patients with HFpEF.
Tell me about this broader project.
(09:33):
You were one of three centersworking on this $15 million project.
So, it's really been one of my, uh,greater privileges to establish a
really close and strong, professionalrelationship with a Dr. Matt
Feinstein here at, Northwestern.
He's a cardiologist, in the Departmentof Epidemiology and he's really reached
across the aisle, so to speak, fromthe, clinical domain to the basic
(09:55):
research is, which is where I live.
And through these interactions bridgingclinical research and insight with basic.
Biology, we've really been able to notonly come to this discovery, which was
published in circulation, but also workclosely to secure funds and support from
the American Heart Association, with anumber of other investigators in this
strategically focused research network.
(10:16):
and through Matt's collaboration andleadership it's, it's really fueled
the next set of questions that cantake our fundamental findings into
the, to the next level of translation.
In the meantime though, there is amessage from this study about diet.
We all know that a diet is key topreventing chronic diseases, but what
was specifically found in this studythat maybe we could all take away
(10:39):
as we look and how to improve ourdiets to prevent diseases like hpe.
The particular types of lipidspecies that were implicated in this
uh, stem cell activation signaturethat, Dr. Philip discovered were
of the saturated fatty acid type.
And so, you know, there have been a numberof studies you've probably heard about
on the radio driving into work which,advocate for, you know, certain types of
(11:02):
Mediterranean diets or other diets thatare high in polyunsaturated or fish oils.
And so this is the opposite type oflipid species and a saturated fatty acid,
which is often associated, with obesity.
the trick is that.
The patients with HFpEF have unique,metabolic signatures, and again, the
disease is so heterogeneous, it'shard to pinpoint one particular type
of lipid species at this moment tomaybe suggest, you know, a, a diet
(11:25):
rich in this or that type of lipid.
But, we are getting closer to moreof a holistic understanding of this.
And I, I think futurestudies will not only.
Again, study the immune system, butalso the different types of diets
that are interfacing with the immuneactivation signature for these practical,
daily interventions that we can takewhen we choose the item on our menu.
So we're gonna shift gears a littlebit to talk about another exciting
(11:48):
study your team published this year.
And that was in the journal immunitythat looked at why newborns immune
systems can regenerate heart tissue whileadults cannot tell me about this study.
A kind of cool thing about the laboratoryis because I would say our, our primary
focus is on the immune system andinflammation and how it interfaces
(12:09):
with cardiovascular syndromes isthat we can take our basic studies on
immunity and particular immune cellsand apply this to many different types
of cardiovascular diseases in additionto HFpEF, which I just mentioned.
And so this means that we just followthe immune cells into different
types of syndromes, includingmyocardial infarction, associated
heart failure, and also even solidorgan allograft, heart transplant
(12:30):
rejection in this particular case.
An answer to your question really,the Holy Grail, uh, for heart
disease is cardiac regeneration.
There was a study, many moons ago from,another group in Texas that identified.
when, uh, newborns have a high capacityfor cardiac regeneration and sometimes
even kids who are, uh, being treatedfor congenital syndromes in the
(12:53):
heart even after surgery, they have alesser incidence of cardiac fibrosis.
kids are just better at healing.
And you and I all know this, that, youknow, when we were young, if we had some
type of injury, we bounce right back.
And unfortunately as we getolder, that's less the case.
But going into the kind of deeper kind ofmolecular aspects of this study, we again.
Investigated how metabolism interfaceswith the immune cells, and how
(13:17):
immune cells and their metabolismof a particular lipid species called
arachidonic acid, was able to bemobilized to promote cardiac regeneration.
And so what was interestingis that a particular immune
cell called a macrophage.
Macrophage is from the Greek word meaning.
large eater.
So macrophage, big eater phage,uh, these macrophages when they
(13:38):
respond to injury in the heart.
In experimental models, in youth inearly days after you're born, they
secrete factors derive from thesearachidonic acid lipids that communicate
with neonatal cardiomyocytes andpromotes cardiomyocyte proliferation.
what's important is that all of thesepathways are turned off in adulthood.
And so, even at first approximation, thesestudies may seem very fundamental because,
(14:02):
you know, there aren't that many kids thatwe know of that have this type of injury.
Although this could be relevantto many congenital disorders.
This is important because it basicallytells us what we need to do to reverse
the condition in aging by potentiallyrestoring what we see in youth.
And, just kinda a last point, we'vebeen really fortunate to L urie
Children's Hospital, also on thisstudy, and a talented physician
(14:24):
scientist, Pediatric Critical CareDoctor by the name of Amanda Becker.
And this paper also is important forme to mention, was led by another
a really brilliant scientist bythe name of, Dr. Connor Lance.
Tell me about all of these differentpartnerships you have and how working with
these physicians and the clinical side hasreally shaped the trajectory of your lab.
(14:46):
A lot of, it's verypractical here at Feinberg.
You can walk across the street andyou can be in the cancer center.
You can be in the cell biology center.
You can be be over at theBloom Cardiology Institute.
And so this, proximity, has reallyenabled, more interactions that are real
and that can lead to, real collaborations.
And because again, we studied theimmune system, the immune system
(15:08):
goes throughout your body and itaffects every type of disease.
There's hardly a condition that Ican think of in which inflammation
driven by immune cells is not.
A part of the pathophysiology.
And so, what's also interesting is thatsome of our molecular mechanisms that we
investigate uniquely affect the diseaseoutcomes that when we just simply study
(15:29):
them in different types of syndrome.
So for example.
one immuno metabolic mechanism maybe protective in cardiac regeneration
through immune cells, but itmay be maladaptive in the adult.
And so this is the beautyof just studying biology.
You just follow the science and, uh, eventhough you start out with a hypothesis,
typically, at least in my case, you know.
We're proven wrong, but it's, it'sbecause the system is so complex over, you
(15:51):
know, hundreds of thousands of years ofevolution that it's really true discovery
and fun to just see what the naturalbiology and physiology is teaching us.
and in a disease relevance way.
We have to have a focus and our focus isreally the immunology and cell biology.
But that naturally plugs into a lot of, relevance in
many different disease states.
So what can we look forwardto from your lab, let's say in
(16:13):
the next year, next five years?
What do you hope to see happen?
So, uh, in addition to continuingthe, fundamental research, which
takes us into many differentdirections, we're very excited about
some of our recent findings that.
Should be published soon, in whichwe've discovered immune roles
for, uh, immunological tolerance.
So, for example, when you havea heart transplant, after your
(16:34):
heart fails, sometimes you are acandidate for a heart allograft a
heart transplant, unfortunately,these transplants can reject.
And so it's very important to educatethe immune system, to educate your immune
system to recognize these foreign heartsas self so that, they're not attacked
upon like, A foreign bug or virus.
But.
(16:55):
It would be nice and helpful tolearn the fundamental mechanisms of
how to educate the immune system,to tolerate the immune system, to
accept these foreign allografts.
And if we can do that, promoteimmunological tolerance at a fundamental
level, think that there's gonna be a, alot of potential to prolong allografts
cardiac and other organs as well.
(17:16):
Well, that's very exciting.
As you said, a completely differentfield of medicine, but again,
all within that wheelhouse ofimmunology and the immune system.
So thank you for sharingthose exciting updates.
One more question before we wrap up today.
as you mentioned, you've receivedsignificant funding from the
NIH over the years and, other,federally funded resources.
(17:37):
So how is the current fundingclimate affecting your lab's work?
Is it affecting yourwork or future projects?
Yeah, I, I won't sugarcoat it.
It's, uh, it's been a, it's been asignificant challenge and this is
where we are very thankful to whatNorthwestern University in Feinberg is
doing right now to support the mission.
I. Of,, our laboratory and manyother of my colleagues here at
(17:58):
Feinberg and up in Evanston.
I've been very grateful to receive,continuous funding from the National
Institutes of Health over the years,and specifically the N-H-L-B-I or
National Heart, lung and Blood Institute.
and I'm hoping and optimistic that we'llcontinue I do wanna advocate if possible,
for the, the basic scientists out therethat, a lot of our clinical and molecular
(18:19):
targets that you know, we're working onreally start from fundamental questions
and basic biology and, and sometimesthat don't immediately have clinical
kind of mindset to, to begin with.
And so, we're optimistic forthe future and doing our best.
We're also, stratified with our fundingsupport through other institutes,
including, as you mentioned, the AmericanHeart Association for which we're
(18:39):
thankful for, and also Department ofPathology, and also of course, Feinberg.
And so we're just gonnacontinue to do our best.
That's all we can do.
I'm really thankful to my laboratoryfor, in this unprecedented climate
to continue to, keep focused and'cause that's all you can do.
Thank you again, Dr. Edward Thorp.
It was a pleasure to have you on theshow to hear more about your research
(19:00):
and all of the exciting things ahead.
Thank you Aaron.
You can listen to shows from theNorthwestern Medicine Podcast
Network to hear more about the latestdevelopments in medical research,
health care, and medical education.
Leaders from across specialties speakto topics ranging from basic science to
(19:20):
global health to simulation education.
Learn more at feinberg.
northwestern.
edu slash podcasts.
This is Breakthroughs, a podcastfrom Northwestern University
Feinberg School of Medicine.
I'm Erin Spain, host of the show.
Each year, more than 800,000 Americanssuffer a heart attack, and many
of those who survive are left withirreversible scarring, and the slow
progression towards heart failure.
(00:31):
Today's guest, Edward Thorp.
Exploring how immune cellsinfluence the heart's ability
to heal after such injuries.
Uncovering fundamental molecularmechanisms by which the immune system
regulates wound repair, inflammationresolution, and tissue regeneration.
He is the Frederick Robert Zeit Professorof Pathology here at Northwestern,
(00:51):
and I am happy to have him on the showto talk about his research that is
helping to pave the way for the nextgeneration of cardiovascular therapies.
Welcome.
Hi, Erin.
Thank you so much for inviting me.
Very happy to be here.
So let's start off by telling me aboutthe focus of your lab and how you began
studying immune cells and inflammationin the context of heart disease.
(01:14):
Yeah, happy to Aaron.
Thanks for the, the question.
My fundamental basic training isin, microbiology and immunology,
actually right here in Chicago.
My lab study is really the fundamentalbiology of immune cells and their role
in inflammation and tissue injury.
Now, typically when people hearabout immunity, they first think
(01:34):
about, you know, immunity againstinfection, bugs, viruses, and COVID.
But it's really important to know that.
your immune system performs other keyfunctions besides combating infection.
For example, your immune cells oryour white blood cells or leukocytes
are critical for tissue repair afteryou scrape your knee and for example,
and, and tissue repair declines,unfortunately, as we age, and we can
(01:56):
all see this, uh, as we get older.
So a major focus of the laboratory is touncover how immune cells regulate tissue
repair and tissue regeneration now.
in addition to our, our basicscience research, we also perform,
clinically relevant, research.
And our clinical, uh, research focusis inflammation during cardiovascular
disease and heart failure.
(02:17):
So, for example, hundreds of thousandsof people each year suffer heart
attacks or myocardial infarctions,and after mi. Or a heart attack
your immune cells or leukocytes arecritical for clearing out the injury
and orchestrating a scarring response.
The trick is that, uh, your leukocytesdon't do a very good job, and this
is because, uh, your immune systemhas evolved mostly to protect us
(02:40):
during our childbearing years.
So we're living much longer now, and soour leukocytes are being exposed to new
types of disease, including heart failure.
And so this is actually a bigopportunity to translate our
fundamental science, uh, into therapy.
And so we're fortunate to do researchhere at Feinberg School of Medicine,
where we work very closely withphysicians and physician scientists
(03:03):
to investigate and translate andimplement therapies, , for disease.
Heart failure with preservedejection fraction or HFpEF.
This is a condition that accounts formore than half of heart failure in the us.
Can you tell me about this condition?
What makes it so challengingto treat and how you've, paired
with other investigators at themedical school , to look into this?
(03:26):
Yeah, good question.
And, and as you mentioned, um, Heartfailure with preserved ejection
fraction or HFpEF, is really themost prevalent type of heart failure.
in fact, sometimes it's called,huff puff because, uh, it.
Causes a shortness of breathand, and exercise intolerance.
And, and so look, I'm not a physicianand HFpEF is a, a technical term, but
(03:47):
what it really does mean for the layaudience is that the heart is fine in
its pumping capacity, but it can't fill.
Properly.
And so the results, uh, means thatyou have reduced, blood supply to
the rest of your body and some of theconditions that are associated with that.
So, despite the prevalence and theimportance of this syndrome there really
are very limited, uh, treatment options.
(04:08):
And so research into thisarea is very ----important.
Yes, because as you said earlier,this really is a disease of aging and
people are living longer now, and thisis something that a lot of people at
Northwestern and beyond are focused on.
HFpEF is definitely a disease of aging, asyou mentioned, and aging is a important,
uh, risk factor for its pathogenesis.
(04:29):
Other risk factors include obesity,metabolic syndrome and hypertension.
And so there is a large need inorder to understand and treat
this very heterogeneous syndrome.
And so, kind of delving a littlebit deeper into the focus of
our, our research and how thatinterfaces with this syndrome.
We've known for years that,HFpEF is associated with, , a
(04:50):
generalized inflammatory syndrome,inflammatory activation in the body.
What we didn't know.
Uh, however precisely is thecontribution and source of this
inflammation during disease.
And so this was a question of Dr.Mallory Philip in the laboratory
when she was a graduate student.
And this was also a collaboration withDr. Sanjeev Shah here at Northwestern,
(05:11):
who's an international expert inheart failure and heart failure
with preserved ejection fraction.
Mallory also worked closely withanother physician scientist, uh, Dr.
Matt Feinstein, who's also an expertin cardiovascular inflammation.
so in this new study published inCirculation, your team looked at how
fatty acid metabolism and immune cellscan drive blood stem cell activation
(05:33):
and heart failure , or HFpEF.
Tell me about this study and the results.
What did you find?
Absolutely.
So, Mallory really was the,the key driver of this study.
And what she discovered was thatpatients with HFpEF had a very unique
immune signature, uh, in their blood.
Uh, specifically, uh, patientshad an elevated immune stem cell
(05:56):
or progenitor cell signature.
And what this means isthat patients actually had.
A very early stage activationof their immune compartment.
Now, property of immune stemcells is that they can generate
many more progeny immune cells.
And so in this context it's reallyimportant to point out that,
immune activation to a certainextent is good and protective.
(06:16):
But if you have too much inflammation,for example, activation of these stem
cells, this can actually do harm.
So, for example, too many leukocytesthat infiltrate the heart can lead to,
unnecessary scarring response, which canimpair the ability of the heart to relax.
I will add, you know, a little bit of asa basic science, uh, test a little bit of
the underlying molecular mechanism that.
Mallory discovered in getting toyour point about the fatty acids.
(06:38):
so in addition to discovering thisfundamental,, insight and into
increased, stem cells during thiscondition, she also studied how the
stem cells were being activated.
And it's really important to pointout that these fundamental questions
are really important in revealingnew molecular therapeutic targets.
So a risk factor for Hef.
Path is obesity or high body massindex, as well as disturbed metabolism
(07:01):
and aging, as we mentioned earlier on.
And typically we think about metabolismas contributing to energy demands, right?
However, how metabolites canalso regulate immune cell.
Function that is separate fromjust energy is really kind of a
cutting edge area of research thatwe don't know too much about now.
And so what Mallory discovered inthis context with that increased fat
(07:22):
and lipids, uh, in these patientswe're capable of reprogramming the
genetic architecture or the geneexpression, in these immune cells to
activate stem cell growth factors.
so to test the therapeutic principle ofher findings, she employed an experimental
model I. Of this disease to block the fatuptake specifically in the immune cells.
(07:44):
And really impressively, she wasable to improve cardiac function
by this immune targeting approach.
Now this is promising, uh, becauseit's much easier intractable to target
your immune cells in the blood ratherthan invasively target the heart.
So what's next with this project?
You've published theseresults in animal models.
Where, what, where do we go next?
Yeah, absolutely., That's, youknow, the million dollar question.
(08:07):
And I think to translate these findingswe would really like to leverage some of
the expertise that's here at Feinberg andalso in Evanston and the really talented
bioengineers who are able to engineerplatforms and molecular targeting to.
Really try to, uh, block this, uh, immunometabolic pathway that's wreaking so much
havoc on immune cells and, and the heart.
(08:29):
And so we've been fortunate to,initiate collaborations with a Dr. Uh,
Lisa Ti and Dr. Pang Zang Pang beingat Feinberg and Lisa up in Evanston.
And so I really.
Think this is the next phaseof the translational work.
But I also, you know, really alsowanna stress as a, as a basic scientist
that we also are informed for clinicalapproaches with through the basic science.
(08:52):
And so really, uh, a main.
Another parallel main focus of thelaboratory is this, again, intersection
again, a metabolism and immune function.
And I won't get into the weedsof the, metabolic pathways, but
we've also been fortunate tocollaborate with investigators here
at Northwestern, including, uh,Nadel and Sam Weinberg for this.
And so really a lot that wedon't know about how metabolism
(09:12):
and metabolites regulate immunecells and their function that's
independent of their energy functions.
And this is particularly importantin cardiovascular disease where
these diseases are often accompaniedby a number of metabolic syndromes.
So this paper is part of anAmerican Heart Association
initiative investigating the role ofinflammation in patients with HFpEF.
Tell me about this broader project.
(09:33):
You were one of three centersworking on this $15 million project.
So, it's really been one of my, uh,greater privileges to establish a
really close and strong, professionalrelationship with a Dr. Matt
Feinstein here at, Northwestern.
He's a cardiologist, in the Departmentof Epidemiology and he's really reached
across the aisle, so to speak, fromthe, clinical domain to the basic
(09:55):
research is, which is where I live.
And through these interactions bridgingclinical research and insight with basic.
Biology, we've really been able to notonly come to this discovery, which was
published in circulation, but also workclosely to secure funds and support from
the American Heart Association, with anumber of other investigators in this
strategically focused research network.
(10:16):
and through Matt's collaboration andleadership it's, it's really fueled
the next set of questions that cantake our fundamental findings into
the, to the next level of translation.
In the meantime though, there is amessage from this study about diet.
We all know that a diet is key topreventing chronic diseases, but what
was specifically found in this studythat maybe we could all take away
(10:39):
as we look and how to improve ourdiets to prevent diseases like hpe.
The particular types of lipidspecies that were implicated in this
uh, stem cell activation signaturethat, Dr. Philip discovered were
of the saturated fatty acid type.
And so, you know, there have been a numberof studies you've probably heard about
on the radio driving into work which,advocate for, you know, certain types of
(11:02):
Mediterranean diets or other diets thatare high in polyunsaturated or fish oils.
And so this is the opposite type oflipid species and a saturated fatty acid,
which is often associated, with obesity.
the trick is that.
The patients with HFpEF have unique,metabolic signatures, and again, the
disease is so heterogeneous, it'shard to pinpoint one particular type
of lipid species at this moment tomaybe suggest, you know, a, a diet
(11:25):
rich in this or that type of lipid.
But, we are getting closer to moreof a holistic understanding of this.
And I, I think futurestudies will not only.
Again, study the immune system, butalso the different types of diets
that are interfacing with the immuneactivation signature for these practical,
daily interventions that we can takewhen we choose the item on our menu.
So we're gonna shift gears a littlebit to talk about another exciting
(11:48):
study your team published this year.
And that was in the journal immunitythat looked at why newborns immune
systems can regenerate heart tissue whileadults cannot tell me about this study.
A kind of cool thing about the laboratoryis because I would say our, our primary
focus is on the immune system andinflammation and how it interfaces
(12:09):
with cardiovascular syndromes isthat we can take our basic studies on
immunity and particular immune cellsand apply this to many different types
of cardiovascular diseases in additionto HFpEF, which I just mentioned.
And so this means that we just followthe immune cells into different
types of syndromes, includingmyocardial infarction, associated
heart failure, and also even solidorgan allograft, heart transplant
(12:30):
rejection in this particular case.
An answer to your question really,the Holy Grail, uh, for heart
disease is cardiac regeneration.
There was a study, many moons ago from,another group in Texas that identified.
when, uh, newborns have a high capacityfor cardiac regeneration and sometimes
even kids who are, uh, being treatedfor congenital syndromes in the
(12:53):
heart even after surgery, they have alesser incidence of cardiac fibrosis.
kids are just better at healing.
And you and I all know this, that, youknow, when we were young, if we had some
type of injury, we bounce right back.
And unfortunately as we getolder, that's less the case.
But going into the kind of deeper kind ofmolecular aspects of this study, we again.
Investigated how metabolism interfaceswith the immune cells, and how
(13:17):
immune cells and their metabolismof a particular lipid species called
arachidonic acid, was able to bemobilized to promote cardiac regeneration.
And so what was interestingis that a particular immune
cell called a macrophage.
Macrophage is from the Greek word meaning.
large eater.
So macrophage, big eater phage,uh, these macrophages when they
(13:38):
respond to injury in the heart.
In experimental models, in youth inearly days after you're born, they
secrete factors derive from thesearachidonic acid lipids that communicate
with neonatal cardiomyocytes andpromotes cardiomyocyte proliferation.
what's important is that all of thesepathways are turned off in adulthood.
And so, even at first approximation, thesestudies may seem very fundamental because,
(14:02):
you know, there aren't that many kids thatwe know of that have this type of injury.
Although this could be relevantto many congenital disorders.
This is important because it basicallytells us what we need to do to reverse
the condition in aging by potentiallyrestoring what we see in youth.
And, just kinda a last point, we'vebeen really fortunate to L urie
Children's Hospital, also on thisstudy, and a talented physician
(14:24):
scientist, Pediatric Critical CareDoctor by the name of Amanda Becker.
And this paper also is important forme to mention, was led by another
a really brilliant scientist bythe name of, Dr. Connor Lance.
Tell me about all of these differentpartnerships you have and how working with
these physicians and the clinical side hasreally shaped the trajectory of your lab.
(14:46):
A lot of, it's verypractical here at Feinberg.
You can walk across the street andyou can be in the cancer center.
You can be in the cell biology center.
You can be be over at theBloom Cardiology Institute.
And so this, proximity, has reallyenabled, more interactions that are real
and that can lead to, real collaborations.
And because again, we studied theimmune system, the immune system
(15:08):
goes throughout your body and itaffects every type of disease.
There's hardly a condition that Ican think of in which inflammation
driven by immune cells is not.
A part of the pathophysiology.
And so, what's also interesting is thatsome of our molecular mechanisms that we
investigate uniquely affect the diseaseoutcomes that when we just simply study
(15:29):
them in different types of syndrome.
So for example.
one immuno metabolic mechanism maybe protective in cardiac regeneration
through immune cells, but itmay be maladaptive in the adult.
And so this is the beautyof just studying biology.
You just follow the science and, uh, eventhough you start out with a hypothesis,
typically, at least in my case, you know.
We're proven wrong, but it's, it'sbecause the system is so complex over, you
(15:51):
know, hundreds of thousands of years ofevolution that it's really true discovery
and fun to just see what the naturalbiology and physiology is teaching us.
and in a disease relevance way.
We have to have a focus and our focus isreally the immunology and cell biology.
But that naturally plugs into a lot of, relevance in
many different disease states.
So what can we look forwardto from your lab, let's say in
(16:13):
the next year, next five years?
What do you hope to see happen?
So, uh, in addition to continuingthe, fundamental research, which
takes us into many differentdirections, we're very excited about
some of our recent findings that.
Should be published soon, in whichwe've discovered immune roles
for, uh, immunological tolerance.
So, for example, when you havea heart transplant, after your
(16:34):
heart fails, sometimes you are acandidate for a heart allograft a
heart transplant, unfortunately,these transplants can reject.
And so it's very important to educatethe immune system, to educate your immune
system to recognize these foreign heartsas self so that, they're not attacked
upon like, A foreign bug or virus.
But.
(16:55):
It would be nice and helpful tolearn the fundamental mechanisms of
how to educate the immune system,to tolerate the immune system, to
accept these foreign allografts.
And if we can do that, promoteimmunological tolerance at a fundamental
level, think that there's gonna be a, alot of potential to prolong allografts
cardiac and other organs as well.
(17:16):
Well, that's very exciting.
As you said, a completely differentfield of medicine, but again,
all within that wheelhouse ofimmunology and the immune system.
So thank you for sharingthose exciting updates.
One more question before we wrap up today.
as you mentioned, you've receivedsignificant funding from the
NIH over the years and, other,federally funded resources.
(17:37):
So how is the current fundingclimate affecting your lab's work?
Is it affecting yourwork or future projects?
Yeah, I, I won't sugarcoat it.
It's, uh, it's been a, it's been asignificant challenge and this is
where we are very thankful to whatNorthwestern University in Feinberg is
doing right now to support the mission.
I. Of,, our laboratory and manyother of my colleagues here at
(17:58):
Feinberg and up in Evanston.
I've been very grateful to receive,continuous funding from the National
Institutes of Health over the years,and specifically the N-H-L-B-I or
National Heart, lung and Blood Institute.
and I'm hoping and optimistic that we'llcontinue I do wanna advocate if possible,
for the, the basic scientists out therethat, a lot of our clinical and molecular
(18:19):
targets that you know, we're working onreally start from fundamental questions
and basic biology and, and sometimesthat don't immediately have clinical
kind of mindset to, to begin with.
And so, we're optimistic forthe future and doing our best.
We're also, stratified with our fundingsupport through other institutes,
including, as you mentioned, the AmericanHeart Association for which we're
(18:39):
thankful for, and also Department ofPathology, and also of course, Feinberg.
And so we're just gonnacontinue to do our best.
That's all we can do.
I'm really thankful to my laboratoryfor, in this unprecedented climate
to continue to, keep focused and'cause that's all you can do.
Thank you again, Dr. Edward Thorp.
It was a pleasure to have you on theshow to hear more about your research
(19:00):
and all of the exciting things ahead.
Thank you Aaron.
You can listen to shows from theNorthwestern Medicine Podcast
Network to hear more about the latestdevelopments in medical research,
health care, and medical education.
Leaders from across specialties speakto topics ranging from basic science to
(19:20):
global health to simulation education.
Learn more at feinberg.
northwestern.
edu slash podcasts.
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