Yes but not least the universe becoming.

And I thank you.

Good afternoon everybody.

I guess as a last speaker I get to
enjoy what everybody else has said and

modify my talk as I go along.

But I am representing Children's
Healthcare of Atlanta and Emory University

and some of the slides have been
talked about by other presenters and

they may not be complete.

So if I've missed anything.

When we do the discussion forums that
will come out in the discussion.

So Children's Healthcare of Atlanta
is a very complicated program.

It spans three sites in terms of
location was a site here about.

Spaulding close to Grady there's
one at Emory main campus and

one up town towards to eighty five and
eighty five and

the director of
the Sickle Cell Program is Dr Lane.

There you are as a clinical director for

children's which includes
a course in a Scottish rights.

Dr Boudreau and Dr G.'s a director for
the six hour program at Spalding but

she's also a member of our group
in terms of sickle cell care.

The names listed here
are people who do clinical

care in terms of patient day to
day care at the three campuses.

We work we talk to act many from Emory and

Grady with the adult program we have
a clinical research office Dr Murray and

our translational research team these are
clinicians last translational physicians

who do both bedside and
a little bit of a bench research and

we have our basic science researchers
listed here again a collaboration between

different parts of Children's Healthcare
of Atlanta Emory University and we have

non He mythology Emory collaborators
we have collaborator Morehouse George

attack Georgia State University other
Sickle Cell Foundation of Georgia.

It's extremely complicated and you can
never understand it when you come for

the first time but it makes sense.

Somehow and we get things done event.

One of our strengths is the fact that
we have about seven hundred patients

in Pediatrics who have sickle cell
disease and that is in addition to

the patients seen at Grady by
Dr Ekman about eleven hundred or

more on and you know we have
inpatient outpatient clinic visits so

there's a wealth of opportunity
to actually translate research

on the bench to individual page
clinical trials at the patient level.

And we divide our research
agenda along several themes and

we try to play to our strengths so
Atlanta has done the most

Boehmer transplants in a single
institution in the country and so

we have a robust Bill Mahr transplant
program where we're looking at sickle cell

and bone marrow transplant both
bat sibling and unrelated.

There's a lot of interest in transmission
medicine in terms of immunization

iron overload and things like that and
for the Translational Research Program

the focus is on undergo and that there are
biology sickle cell kidney bone pain and

strokes and
then we're beginning to develop and

expand our outcomes research I think the
issue of transition falls under outcomes.

The issue of health literacy in
education falls on the outcomes and

expanding the use of Hydrox
around a patient population.

This is just a laundry list of all
the different investigation A studies

are being done and the translation
will slash close clinical arena.

I'm the P.R. on the vitamin D.
sort of has close to a crawl.

I have a study looking at nutrition and
immune function but I actually developed

based on some of the work that out to him
or has done or not as eager Emory as some

of my mentors Dr Dampier is working on
quality of life is a nice funded study.

Dr G. has been mentioned before under
the Morehouse program Dr G. and

Dr Hiper it have been mentoring a post-doc
who's looking at the barrel development of

sickle cell disease and then we have
a program sickle cell kidney disease

that actually has been put forward by the
Sickle Cell clinical trials network but

is chaired by Dr Chua she's a kidney
doctor at Emory Dr Brown one of

our pediatric mythologists is looking at
brain mapping in terms of how does your.

Brain responds to sickle cell
disease in terms of function.

Compared to controls compare has been
talked about before with the Morehouse

program the boomer transplant group really
is focusing on how do you reduce graphics

are supposed to Z's and sickle cell
patients getting transplants and

how do you reduce the risk
of CNS complications and

they start really early in those
from the kinetics of yourself and

with sickle cell G. and T. and
reducing seizures and strokes in the peri

transplant period and then Dr a decent
under Dr for Iraq was mentorship is

working on genetic heritage in the in a Q
chest syndrome and sickle cell disease.

If you want to look at it in terms of
what is the underlying theme and what is

the core factor that guides most of our
physician researches really inflammation.

As regards to kidney disease lung disease
bone marrow technology mine attrition and

bone disease.

I'll immunization and G.H.D.
sickle cell transplant

the bottom line is an inflammatory
disorder and he has multiple different.

Feel to be manifestations of a need
to begin to look at it not just in

the laboratory but
also on the patient level and

understand how inflammation impacts a
clinical phenotype of sickle cell disease.

These are some of the studies that
have been published by our group.

Dr.

Lamb is in the audience this was talked
about before Dr doctor for up was Lab

presented data on the vascular mediators
of injury in sickle cell disease.

I so just since I am presenting for
children.

Am I get to talk about my research
a little bit more than everybody else's.

It's all about me.

But I notice very early on that in my
patients with sickle cell disease they

have very low vitamin D. levels and that
was the impetus for my research agenda and

what came from that was looking
at what their levels are and

if you spend the spectrum.

Most of them are below the level of thirty
which is where you defined sufficient.

OK And a clinical observation where
a patient we are very profound vitamin D.

deficiency responded very
dramatically to vitamin D.

supplementation and her pain resolved and
actually has been hospital.

Free pain free and
medication free for the past.

I think is going on for years now.

This is very exciting but

it kind of led to the question why is
this happening how does it happen.

What else is going on and what are the
other effects of vitamin D. deficiency and

so my initial evaluation on
sickle cell disease or vitamin D.

I looked at you know what are the markers
of Army deficiency not sickle cell

patients and how do I relate
that to sickle cell disease.

Well if you look at the bones
in terms of bone fragility.

I did this is published in British Journal
of hematology where you noticed

bone fragility sickle cell disease is
related to the level of vitamin D..

In your in your serum.

So it's not just how if you're low but

how low are you will determine your
determine your bone disease severely

as well as your level of chronic
pain versus non chronic pain.

And so you know you want to look at OK
well how is the how does this work was

a pathophysiology Well Vitamin D.
is a mall Tice's Stanek is a hormone that

affects every single organ system in the
body and if we put this as our benchmark

to look at these organ the sickle cell
disease we know that there are different

areas of this is I'm affected by
a material status and a vitamin D.

level and so I have a pilot study that's
ongoing right now looking at Vitamin D.

to improve sickle cell chronic pain.

There's another one looking at
a nutritional status in general I'm sorry.

First.

On it.
OK the traditional status and

immune function and information is sickle
cell disease this is something I'm going

to be looking at in the future this in
the wrong location actually should be for

the down but other vitamin D. effects so
what does it do to the long queue chest

syndrome or
prevalence of chronic lung disease.

What does it do to depression acute and

chronic pain and physical activity you
know that your muscle strength and

function is impacted by your vitamin D.
status.

And then of course Dr Hibberd and
doctors ago were instrumental in me.

Coming up with this proposal looking at
your baseline which is not status as much

as vitamin D. But I mean zinc
retinol Solenn the I mean how do

these impacts your sickle cell phenotype
be the immune function immune infection.

On.

That is stress etc.

As part of that study we have looked at
some baseline information on sickle cell

disease immune function terms of
quantitative immune profiles and basically

we're finding that patients with sickle
cell disease have higher white counts

all different varieties compared to six
months ago so controls they have higher T.

cell and B. start counting the prayer for
a blood and they have a higher

ratio of C D four to see the eight counts
and these are also physically significant.

And we're going to go on for the to
look at what does this mean to function.

So are they function really him
incompetent in spite of these numbers or

does that impact their immune type.

When you look at.

T.M.B. lymphocytes in terms of their
percentage is there is a skewing of.

The phenotype towards more B.
cells and T. cells and

these are opposed to significance but
I thought this is very interesting.

I haven't seen this in the literature
before the higher prevalence of.

This is another slice see
the double C double negative.

T. cells and in sickle cell
patients compared to controls and

this is typically significant.

Thank you.

Cells there was no there was
not much of a difference but

really they had most of
the toxic cells and.

Not so toxic.

Cells.

All right so
going forward what are we going to do be

again thrusting on information what
are the different markers of approach

from a terrific fibrosis an answer from
a different type and how does that affect

your redux status your micronutrient
status and your metabolic him and

your pain and really what comes from the
chicken or the egg we're not quite sure.

And my job is to take what
has been done in the lab and

bring that to the patient and

figure out if we can make sense of what's
going on and we do an intervention that

will improve that Dr Lamb star stuff has
been talked about by two different people.

So I won't go into that
this is Dr HENDRICKS and

who is her work is on our immunization and
she really believes that your inflammatory

profile increases your risk of having our
antibodies in sickle cell disease patients

compared to controls and
those would say and she's also one of our.

Sickle cell docs Dr.

David Archer is looking at sickle cell
kidney disease and he has documented.

You know blood flow is higher in trace and
Nonsuch So this is going to

sickle cell disease in the sickle mouse
far is lower in sickle cell disease and

your undercover crime in Clarence is
more elevating the success of this

economy to controls and
this is some of his article in the idea.

Dr Dampier is looking
at outcome measures for

sickle cell disease quality of life and
this study called Promise tested.

Validation of twenty two hundred thirty
three patients with sickle cell disease

from eight to seventeen years in terms
of depression anxiety pain fatigue

upper extremity strength and dexterity and
their mobility and when there is

a specific difference isn't one of our
other faculty Dr new has been in the K.

or seven that we're hoping we think will
get funded looking at specific mark.

Tools for
sickle cell disease that would be

that would validate what he has
found with the promise study.

So the bottom line is we take care of
patients Well I think our patients and

I can't forget the reason
why we're doing this and

this is what I see in the clinic and this
is what leads me to ask the question as to

how can we do a better job with
treating sickle cell disease.

We see increased hyperplasia.

We see like also as we see
compression spine fractures and

then the bottom line is there
are people behind these pictures so

I have this is a sickle
cell teen girl guy talk and

girl talk where a doctor because of this
it's up to the younger people sickle cell

disease to help them to get you know
understand what life is like for

them as they get older and
that they will get older and so

they're living longer with their in the
six seven and eight decade there really

is a need to figure out how do you
translate what's happening at the bench

to the patient and it's not just
the patients this is a patient.

This is not a sickle cell piece by his
siblings has a cause autism they all died

and his brother was a friend
of mine from medical school.

He was to be thirty five and I think and
I think you know we talked together and

Mike is going to be more than we
can offer sickle cell patients.

Now than we did in the eighty's and
the ninety's.

And a plug for Education Day in
September on the seventeenth.

And I'm open for questions.

Thanks.

Yes.

So we are going to look at functional
markers that's part of my training

plan from my K. Grant and so
one of the things we're thinking

about is it just a number issue
was it actually an activity and

a functional issue so over the next
to the data we're going to look at is

functional markers of white cell and
Target is so difficult.

I tell us is he met with the nation and
things like that.

And Dr King who works with and
I'm a group is also on my mentoring team.

Yes.

And so one of the thoughts is that

you have a hyper metabolic state
was sickle cell disease and

that that's one of the reasons why
they tend to have low vitamin D.

levels and other vitamin levels but if you
look at the African population as well.

They have low vitamin D. levels.

It's partly diet.

It's partly that they don't make it in
their skin because of pigmentation but

there is some data and I think it's
from Morehouse about increasing our

loss of vitamin D. So
we're looking at human loss of vitamin D.

in our patient population and we're
looking at sickle cell patients sickle

cell siblings who don't have similar
success people who don't have to go.

So this is and then nonce to bling
African-American controls and we're going

to look at those three groups to see if
they make some sort of understanding.

Plus there's a vitamin D.

put in morphism that may impact
the way you metabolize vitamin D.

and how it's handled in the kidneys so
we're going to look at all that as well.