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Shyamala Dakshinamurti MD, MSc, FRCPC, FAAP

Currently accepting students.

Current Position

Associate Professor, Pediatrics, University of Manitoba; Adjunct Professor, Physiology, University of Manitoba; Coordinator of Neonatal Research, University of Manitoba

History

Dr. Dakshinamurti is a neonatologist and biomedical researcher at Children’s Hospital Research Institute of Manitoba, and Associate Professor of Pediatrics and Physiology at the University of Manitoba. She received her MD in 1992 from the University of Manitoba, worked briefly as a general practitioner in Canada and volunteered in India, before obtaining her General Pediatrics training at the University of Chicago and a fellowship in Neonatology at the University of Manitoba. She joined the U of M faculty in 2001, completed an MSc in Smooth Muscle Physiology under the guidance of Dr Newman Stephens in 2003, and started the Neonatal Pulmonary Biology lab in 2003 as an independent clinician scientist. She is a member of the Biology of Breathing research theme, and the DEVOTION research cluster, dedicated to the developmental origins of cardiopulmonary disease. Dr.Dakshinamurti is Coordinator of Research within the Section of Neonatology, organizes the annual international Dr. JM Bowman Symposium on Neonatal Research, and functions as Research Director and Scholarly Oversight Committee Chair for the University of Manitoba’s Neonatal/Perinatal Medicine Fellowship Program. Her areas of research interest are pulmonary hemodynamics during circulatory transition, and the physiology and pharmacology of vascular smooth muscle in the neonatal pulmonary circuit.

2003 MSc Physiology, University of Manitoba
2001 Neonatology fellowship, University of Manitoba
1998 Pediatrics, University of Chicago
1992 MD, University of Manitoba
1989 BSc University of Winnipeg

Research Focus

There are more ‘moving parts’ at the moment of birth, than a human being has to regulate at any other point in life. And sometimes this complex process can go very wrong.

During pregnancy a baby’s mother provides oxygen, so the blood vessels in the baby’s lung are unused and tightly constricted. Rapidly following birth, the lung blood vessels must relax and dilate to accommodate blood flow, allowing all the blood to flow through the lung to pick up oxygen during breathing.

Soon after a baby is born, with its first breath, air rushes into the lungs – so in order to pick up oxygen from that breath, blood urgently has to flow to the lungs too. The trigger for this essential rush of new lung blood flow is oxygen, and time is of the essence. During a difficult labour, a baby can become very short of oxygen; and sometimes after a difficult birth a baby has difficulty taking its first breath. In lungs of otherwise healthy infants who undergo difficult deliveries or can’t get those critical first breaths, lung blood vessels don’t see the oxygen in time, so they fail to relax. These babies don’t have enough blood flowing to their lungs. So even when they try to breathe, they can’t pick up oxygen from their breaths – and they stay blue. This lethal disease is known as Persistent Pulmonary Hypertension of the Newborn (abbreviated PPHN). It happens in up to 6 per 1000 births, accounts for up to 10% of admissions to the newborn ICU, and these “blue babies” are the sickest in the newborn ICU. If untreated, PPHN can kill in hours or days.

We’re looking for new ways to treat these babies, to help their lungs relax to allow blood flow, and to help their hearts pump against the burden. The current treatment of choice for PPHN is inhaled nitric oxide. Some babies are simply unable to respond to this medication. Most of these babies have associated inflammation of the lung. The muscle cells in their lung blood vessels begin to grow out of control, thickening the walls of arteries and creating an irreversible obstruction to blood flow.

In the Neonatal Pulmonary Biology lab, we study the effects of insufficient oxygen at the time of birth on the normal process of relaxation of the walls of lung blood vessels. In an animal model of pulmonary hypertension, and also in arterial muscle cells grown in low oxygen levels, we are trying to determine how molecules released in inflammation (known as prostanoids) interact with a low oxygen environment, preventing proper responses to medical therapy. We are examining how muscle cell growth in lung arteries is regulated, and how long we have before fast-growing muscle cells can make medical therapy futile. To study this, we have developed a model of the pulsing arterial wall, using muscle cells grown on a membrane that stretches like a newborn heart beats. We are also studying the effects of low oxygen levels on the function of the heart, and on muscle lining the blood vessels of the newborn lung. Heart muscle and lung blood vessel muscles have opposite jobs at birth. The heart needs to contract harder, and lung blood vessels need to relax to let blood flow. These opposite events happen through a single system of signals inside the cell, called the adenylyl cyclase pathway. We found that exposure to a low oxygen level makes the adenylyl cyclase enzyme slow down – like a foot on the brake of a car. Many important drugs use the adenylyl cyclase system, including those we use in the ICU to make a baby’s heart pump better. We hope to make such medications work better in PPHN.

We believe that a better understanding of this crucial process in the newborn lung can help us improve options for treatment of PPHN, and in every tiny patient, reverse the disease before it becomes untreatable.