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Professor
Dr. Nateetip Krishnamra was born
on June 1, 1951 in Bangkok. She received
her primary and the first phase of
her secondary education Wattana Withayalai
School in Bangkok before going for
further education at Ashford School,
Kent, England where she completed
the G.C.E.O'levels and A'levels. She
received her B.Sc. in Biological Sciences
with first class honours from Westfield-Queen
Mary College, London University in
1974. After returning to Bangkok,
Professor Dr. Nateetip Krishnamra
joined the Department
of Physiology, Faculty of Science,
Mahidol University as a staff member
in the same year. This was where she
received her graduate training under
the supervision of Professor Dr. Liangchai
Limlomwongse, and received her M.Sc.
and Ph.D. degrees in physiology in
1977 and 1980, respectively. She was
awarded a Ph.D. student award from
the Professor Tab Nilanithi Foundation
in her first year of the Ph.D. programme.
Professor Dr. Nateetip Krishnamra
was appointed Assistant Professor,
Associate Professor, and Professor
at the Department of Physiology in
1981, 1987, and 1996, respectively.
She has been teaching cell physiology
and endocrine physiology to second-year
medical students of the Faculty of
Medicine, Ramathibodi Hospital, and
to graduate students, and has published
34 international papers and 10 local
papers from her work on calcium and
bone metabolism. As for administrative
experience, she served as Deputy Dean
for Policy and Planning for 2 years
(1999-2000) during Professor
Dr. Amaret Bhumiratana's term
as Dean of the Faculty of Science.
She has also served ad Vice President
of the Mahidol University Senate (2004-present),
and is a member of the Mahidol University
Committee for Academic Ranking and
Positions (2000-present). She also
received the Faculty of Science's
Best Teacher Award in 2002, and a
Senior Research Scholar Award from
the Thailand Research Fund in 2004.
Professor Dr. Nateetip Krishnamra
is married to Professor Somroek Krishnamra;
they have a son, Somkrit.
Professor
Dr. Nateetip Krishnamara's interest
in the body regulation of calcium
metabolism was initiated during her
dissertation years when she studied
the effects and mechanism of action
of gastrin, a gastric hormone, on
the intestinal calcium absorption
and the regulation of plasma calcium
concentration. Her research topics
shifted in the following years to
the study of prolactin, the milk-producing
hormone from the anterior pituitary,
and calcium metabolism. At the same
time her work broadened to cover new
organ systems such as bone, which
is a novel target of prolactin. With
her background as a physiologist,
Professor Dr. Nateetip Krishnamra
strongly believes that a complete
understanding of the function of a
hormone or any biomolecule requires
experimentation at he systemic or
whole body, organ, tissue, cellular,
and molecular levels. Thus her research
publications demonstrate a systematic
approach to problem solving using
in vivo, in situ, and in vitro techniques.
Discipline-based investigation such
as physiology, biochemistry, of molecular
biology alone cannot provide conclusive
answers to biomedical questions. This
realization, together with the need
to be able to translate the basic
research findings into clinical use,
helped drive her to form the Consortium
for Calcium and Bone Research (COCAB) at the Faculty of Science in 2003.
Consortium members include researchers
with shared interest in calcium/bone
metabolism from Mahidol University
(Department of Physiology and Biochemistry,
Faculty of Science, and clinical researchers
from the Faculty of Medicine, Ramathibodi
Hospital) as well as researchers from
Srinakharinwirot University, Chulalongkorn
University and Kasetsart University.
The aims of COCAB are to study the regulation of bone
remodelling and pathophysiological
processes of metabolic bone diseases
of high incidence in Thailand, such
as osteoporosis, bone disorders associated
with distal renal tubular acidosis
(dRTA), thalassaemia, and fluorosis.
Her current research is divided
into 3 areas as follows:
1. Mechanism of the intestinal
calcium absorption
Investigations in experimental animals
have led to new findings that, in
addition to being classified into
passive and active transport as described
in textbooks, the intestinal active
calcium transport can be further divided
into transcellular, voltage-dependent,
and paracellular solvent drag-induced
active transport, with the last contributing
as much as 75% of the total active
transport. This type is induced by
the transport of Na+ out of the cells
into the intercellular space by Na+-K+-ATPase
creating and osmotic gradient that
eventually drives fluid flow from
the lumen to the blood compartment.
The group is currently engaged in
finding the molecules responsible
for the charge-selective characteristics
of the paracellular transport mechanism.
2. Prolactin: a novel role in
the regulation of calcium and bone
metabolism
Interest in prolactin stemmed from
a report that the high rate of intestinal
calcium absorption in pregnant and
lactating rats was independent of
the vitamin D hormone, 1,25(OH)2D3,
which is known to be the prime regulator
of calcium absorption in non-pregnant
conditions. Since prolactin is the
only hormone with circulating levels
on pregnant and lactating rats, more
than 20 times higher than the normal
level in non-pregnant rats, and it
has been reported to alter transport
of some electrolytes, it was interesting
to find out if prolactin could contribute
to this high rate of calcium absorption.
Her laboratory has shown that prolactin
has both acute and long-term stimulatory
effects on both passive and active
calcium transport, especially in young
growing animals, but not in aged animals.
Moreover the absorbed calcium was
found to be accumulated in bone under
prolactin influence. To find out the
physiological significance of prolactin, Dr.
Nateetip Krishnamra's investigation
shifted to bone. Up until now, results
indicate a role of prolactin in the
regulation of bone growth in the weanlings
and young, and bone remodelling in
mature rats. Since prolactin was also
found to elevate calcium concentration
in milk, it is possible that prolactin
may regulate calcium handling in the
mammary gland.
All of these results led to the
present hypothesis that prolactin
is a novel calcium regulating hormone
that helps synchronize calcium handling
in the intestine, kidney, mammary
gland and bone, in such a way that
calcium is put to use by the body
for bone growth and development in
the young, and for foetal development
and milk production during pregnancy
and lactation, respectively.
3. Disorders of calcium and
bone metabolism in metabolic bone
diseases. This part constitutes
the translation between basic and
clinical research with an aim to find
out the mechanism of pathophysiological
processes in bone that are associated
with osteoporosis and adynamic bone
in RTA patients. The investigation
involves studies in patients, experimental
animal models and cultured primary
cell and cell lines.
Future research will cover these
three areas in greater depth and with
a more integrative approach as follows
:
- To study how the recently discovered
tight junction proteins, claudins,
are involved in calcium absorption,
and how they may be regulated.
- To prove the hypothesis that
prolactin is a novel calcium regulating
hormone that synchronizes calcium
handling in the intestinal cells,
bone forming and bone resorbing
cells, and mammary gland cells.
Under prolactin influence, target
organs work together in such a
way that calcium is translocated
to the foetus during pregnancy,
to mammary glands for milk production
during lactation, and to bone
during growth and development
in the young.
- To find out the molecular and
genetic mechanisms of bone cell
dysfunction in metabolic bone
diseases such as osteoporosis
and dRTA in order to come up with
better methods for diagnoses and
treatment.
- To make use of mathematical
models in the study of calcium
metabolism and bone remodelling
in normal and pathophysiological
condition, ad well as in the prediction
of calcium/bone responses to various
stimuli.
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