My name is Daphne Bell and I’m a basic researcher.
I am Charles Rotimi and I’m a basic scientist.
I’m Julie Segre and I am both a basic and a clinical researcher.
My name is Ed Ramos. I am a research fellow in basic sciences.
My research is to understand the genetic alterations that cause endometrial cancer. This is a cancer
that forms in the womb or the uterus and it kills over 73,000 women worldwide every year.
The research that we do here at the -- at our center here called Center for Research
on Genomics and Global Health is really directed at how we can bring cultural factors and also
genetic factors together to help understand why diseases vary as you go across human populations.
And we pay particular attention to populations of the African diaspora.
My research examines all of the bacteria that live on your skin and how the diversity of
bacteria and the change over time contributes to both health and disease. We use high-throughput
DNA sequencing as a very powerful microscope to identify the bacteria based on their DNA
sequence to complement what we can grow on petri dishes or in liquid culture.
I’m part of a research team that focuses on human genetic variations very generally.
And to really capture the true genetic diversity that you see in present man, we focus on studying
multiple populations, so European ancestry, African ancestry. And we do this in a variety
of different contexts.
My research approach to studying endometrial cancer is to compare the DNA code in the tumor
genome from an individual patient with the DNA code of the normal genome from that same
patient and I compare it over a series of about 100 patients and look for the common
mistakes in the tumors.
Right now, we are now able to query the whole genome. And we are able to query that at reasonable
cost and that is really giving us fundamental knowledge -- fundamental insight into diseases.
For example, we are finding that genes that we thought only related to diabetes to also
related to cancer, for example.
We have a clinical trial for kids who have bad eczema, which is an itchy skin disease.
It often affects kids in the bend of their elbow, behind their knees. But it can happen
-- it can be dry skin on your hands. What we’re trying to explore is the connection
between the shifts in the bacterial diversity and the disease progression.
So the context of our research is in diseases and in drug response as well, so human genetic
variations with respect to disease. We focus on type 2 diabetes, hypertension, and obesity,
and other related traits.
Cancer research has really been turned on its head because now we can look for faulty
genes that are present in tumor cells. We can characterize those faulty genes and understand
how the protein is misshapen or behaves in a different way than the normal protein. And
we can start to develop smart drugs that really target the faulty protein and leave the normal
protein relatively untouched.
What we envision is that we will be able to, from these studies where we look at the longitudinal
data, we will be able to determine some sort of assay that looks -- fast assay -- that
looks at the microbial diversity and says, something like when you test your glucose
levels, you would test your microbial diversity. And you’d test your levels of staph-- pseudomonas
versus propionibacteria. And if you start to get out of balance, then you could use
some sort of pro-biotic or antibiotic therapy to reset a healthy balance of skin bacteria.
So the genome-wide association studies, if you’re successful, you get what we call
hits in terms of variants that are associated with the trait that you’re looking at. So
for my specific research, if I’m looking at type 2 diabetes and I have people that
have the disease and I compare them to people that don’t and something shakes out in terms
of genetic variants and associates with type 2 diabetes, I now can look at, all right,
what gene is that variant in?
Our hope is that this knowledge will be able to translate -- be translated into more effective
tests within the hospital setting that would allow us to match specific patients to specific
drugs. In other words, personalized medicine for cancer.
For me, it’s really an exciting time to be a scientist who wants to understand the
genetics of diseases.
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My name is William A Gahl and I’m a MD PhD, and a pediatrician and a clinical and biochemical
geneticist.
My name is Teri Manolio. I direct the Office of Population Genomics at the genome institute.
I’m primarily a clinical researcher.
I’m Leslie Biesecker and I am a clinical medical geneticist working in the Genetic
Disease Research Branch here at NHGRI.
My name is Dan Kastner and I’m the Scientific Director of the Intramural Research Program
of the NHGRI.
I see patients with inborn errors in metabolism and do clinical research and some basic research
into the particular disorders that our patients have.
At present what we are trying to do is apply genomic technology to population studies.
So that the main focus is to take existing population studies which are usually large
scale, large numbers of people who’ve been followed for a long period of time, initially
perhaps without disease but then developing disease later. And try to apply genomic technologies
to try to determine why they developed those diseases.
My research program is focused on understanding relationship between the genotype and the
phenotype, or the medical or clinical manifestations, in patients and humans in general. And so
we go from the clinic, to the laboratory and understand how the genome makes us what we
are and what we aren’t; makes us healthy or makes us ill.
I am in a way both a clinician investigator and a basic researcher. My interests are basically
in understanding the mechanisms of human disorders of inflammation and understanding how these
diseases come about and what we can do to intervene to help patients who have them.
Having the Human Genome Project and knowing the sequence of all these genes now allows
us a shortcut to that, allows us to find the genes by different mechanisms and because
the function of many of those genes is known we then know immediately what to investigate
in terms of biochemistry and cell biology.
The initial genome-wide association studies really were a big surprise to everyone in
that they started finding things. So people who had been in this field far longer than
I, who’d been struggling for 20 years to find a hypertension gene or whatever and really
had come up with very, very little were thrilled that, you know, suddenly things were coming
up positively.
The ClinSeq Project is a rather ambitious and some may say bold effort to actually take
the genome, take genomics, take a genome center and put it right in the center of a clinical
research program and directly apply high-throughput genomics to patient care research.
So there the technique was basically to go out and find a large cohort of families with
the disease with multiple members of the family with the disease, and to try to compare the
inheritance of the disease in the families with the inheritance of DNA markers of known
chromosomal locations.
I would say that the Human Genome Project has helped enormous numbers of individuals
find causes of diseases, make diagnoses, and now we’re really approaching the therapeutics,
therapeutic interventions in that.
We certainly can in a -- looking at the entire genome -- identify people who are at extraordinarily
high risk. So you may have 20 alleles that put you at risk for type 2 diabetes, most
people have, you know, five, or eight, or ten of them but what if you had all 20? You’re
at much, much higher risk than if you don’t have any.
So I can bring in to the Clinical Center a family with -- a single family with a previously
un-described disorder and within a few weeks understand what the molecular alteration is
that’s causing that disorder. And that’s something that was utterly incomprehensible
15 years ago.
Once one lands in a particular chromosomal region you can simply go to the databases
and look up what genes are there and even have an idea of what their functions are so
that you can very easily cut to the chase and be able to get to the gene that is likely
to be the culprit gene for your particular disease.
I think knowing the Human Genome Project and the sequences of genes and where they are
has already had a great impact on medical care.
In two years we’ll have, I suspect, far more variants that are related to either drug
metabolism or symptoms or signs or prognosis.
We’re already practicing personalized medicine. Simply by taking a patient as we have done,
and sequencing their genome, and finding in their genome a liability to a trait that has
not yet manifested in that person, we can sit with that person, explain what that trait
is, explain what the symptoms are, and then they can be empowered to better manage their
individual health care in the future as it arises.
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