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Email Interview with Bela Anand-Apte, MD, PhD from The Cleveland Clinic
Department: Ophthalmic Research, Cellular and Molecular Medicine
Education & Fellowships:
Fellowship at Harvard University, Postdoc Fellow, Immunopathology
Doctorate - Boston University, Microbiology
Fellowship - K.E.M. Hospital, Immunology Research
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Residency - K.E.M. Hospital, Internal Medicine
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Medical School - University of Bombay, Seth G.S. Medical College
Interviewer: 1) Could you please explain what you do at the Cleveland Clinic?
Apte: I run a research laboratory at the Cole Eye Institute. We investigate a number of diseases
that cause people to lose vision..such as diabetic retinopathy (where people with uncontrolled
diabetes lose vision), age-related macular degeneration (a disease seen in elderly patients who
lose vision), retinopathy of prematurity (a disease that is often seen in premature babies) and
ocular melanoma (a type of eye cancer). We look for why patients lose vision in these diseases
and what can we do to either prevent or cure this vision loss.
Interviewer: 2) What is the significance of James Watsons’ discovery of the double helix to
your field and science in general?
Apte: The discovery of the structure of DNA and the mechanism by which it replicates to
transmit traits through succeeding generations has been invaluable to understanding a number of
diseases.In the field of ophthalmology, it has played a major role in improving our
understanding of a number of diseases that are hereditary. In the past 15 years geneticists have
identified about 500 genes that contribute to eye disease. This is important not just from the
perspective of patients and families to know the risk of getting a disease but also from a research
standpoint. If we know the gene that is mutated in a disease…we can study the difference in
function between a normal protein and a mutated protein and try to find ways to reverse the
effects of the mutated protein. I study an inherited disease called Sorsby's Fundus Dystrophy for
which the gene mutation is known. Patients with this disease have a mutation in a protein called
TIMP-3 (Tissue Inhibitor of Metalloproteinases-3). We examine the functions of normal TIMP3
and see if the mutated protein can perform those functions and how this might cause the disease.
Interviewer: 3) How does your job contribute to genetics in general today?
Apte: While my research likely does not contribute to the field of genetics directly, I use
genetics research to determine how mutated genes contribute to various eye diseases.
Interviewer: 4) Why do you think genetics is important to understand?
Interviewer: 5) What does research in genetics have the most impact on today?
[This response encompasses the answer to both Questions 4 and 5]
Apte: It improves our knowledge of normal and disease states. There is new information being
generated on various ways genes get regulated (i.e. Turned on or off) called epigenetic regulation
of genes. This is now a "hot" field and is being tested in a number of disease states.
Interviewer: 6) We understand that other people also deserve credit for the discovery of DNA,
to you, who deserves the most credit and why?
Apte: I think there were 5 key papers that led to the discovery of the DNA structure
The first was in 1944 by three scientists, Avery, MacLeod and McCarty who showed for the first
time that DNA is the material of inheritance. Prior to that everyone (i.e. Scientists) believed that
"genes" were made of protein.
Following this there were 4 papers published between April and July of 1953 , two by Watson
and Crick . Their first paper described the double helical structure of DNA and they suggested a
possible mechanism for copying of the genetic material. Int heir second paper they accurately
speculated the base pairing mechanism for replication of DNA.
However their breakthrough would not have been possible without the findings of Franklin and
Gosling who showed the helical nature of nucleic acids which suggested that the phosphate
backbone could lie on the outside of the structure. In a paper in July, Franklin and Gosling
detailed the distinctive A and B structures of double helix in DNA.
I do think Rosalind Franklin deserves credit as without her work it might have been difficult for
Watson, Crick and Wilkins to get the idea of a double helix.
Interviewer: 7) Do you know how the DNA structure is affected in the disorders such as
Achondroplasia, sickle-cell anemia, cri du chat, or Tay-Sachs disease?
Apte: Achondroplasia: patients with achondroplasia have mutations in a protein called fibroblast
growth factor receptor 3 (FGFR3). The protein is normally present in cartilage and the central
nervous system..so mutations generally affect these parts of the body. In most patients with
achondroplasia there is a G to A mutation at position 1138 (this is the nucleotide number in the
DNA). This mutation causes a change in the amino acid at position 380 of the protein. Glycine is
changed to Arginine. This small change results in a poorly functioning receptor and the disease.
Sickle Cell Anemia: mutation at position 20 of the beta chain of hemoglobin results in a change
in amino acid at position 6 where glutamic acid is substituted for valine. This leads to atypical
hemoglobin molecules called hemoglobin S which distorts red blood cells into a sickle or
crescent shape. Basically the abnormal shape of red blood cells causes them to break down
prematurely leading to anemia. Importantly this is an autosomal recessive disease which means
that both copies of the gene in each cell should be mutated for the disease to occur. The parents
of a patient with sickle cell disease each carry one copy of the mutated gene and typically do not
show any signs and symptoms of the disease.
Cri-du-Chat is caused by deletion of a portion of the short arm of chromosome 5 which results in
a number of missing genes. The deleted gene that has been suggested to cause most of the
symptoms is telomerase reverse transcriptase (hTERT) gene.
Tay-Sachs Disease is caused by mutations in the HEXA gene that is important in coding for part
of the enzyme called beta-hexosaminidase A. This enzyme is involved in the breakdown of a
fatty substance called GM2 ganglioside. When there is an improper functioning of betahexosaminidase A there is no clearing of GM2 ganglioside and accumulation to toxic levels in
the neurons in the brain and spinal cord leading to the destruction of axons and symptoms of the
disease. This is also an autosomal recessive disease.