Dr. Kajana Satkunendrarajah
Associate Professor Medical College of Wisconsin
Postdoctoral Researcher Krembil Research Institute
PhD Wayne State University
Dr. Kajana Satkunendraraja deeply appreciates the complex orchestration required for the body to achieve its desired movement. From the East Indian Classical dance she has performed since she was three, to her current research on the neural networks underlying motor behaviors in the brain and spinal cord, Kajana has always been drawn to movement. As an Associate Professor in the Departments of Neurosurgery and Physiology at the Medical College of Wisconsin, Kajana operates at the intersection of basic research and translational science. Her lab studies the neural basis of movement and the mechanisms of novel treatments for spinal cord injury and degenerative motor disease.
Growing up in Toronto, Kajana was ambitious about her education and thought she would be an engineer like her father. However, when she was first introduced to body systems in a high school biology class, she became fascinated by how living things function. After finishing her undergraduate studies in biology at the University of Manitoba, Kajana decided to pursue a PhD at Wayne State University in Detroit, Michigan. Her PhD research in the lab of Dr. Harry Goshgarian focused on the spinal cord, specifically how networks of neurons in the uppermost segment of the spinal cord, the cervical spinal cord, were responsible for an essential biological process: breathing. The cervical spinal cord is also the most common site of traumatic spinal cord injury, with 50-60% of injuries (like car crashes and falls) damaging this vital segment. When injured, the cervical neurons innervating the diaphragm are damaged, leading to impaired breathing in addition to the muscle paralysis most commonly associated with spinal cord injury. During her PhD, Kajana built upon previous work in the lab on how these interrupted pathways can be repaired after injury by promoting plasticity with a molecule called theophylline. Theophylline is traditionally used as a medicine that relaxes the air passages in the lungs, but in the context of spinal cord injury, it leads to increased neural growth. However, it was still undiscovered how or why theophylline helped. To investigate this mechanism, she used electrophysiology and pharmacological techniques on cultured cervical spinal cord neurons and found that cyclic AMP, an essential signaling molecule, is upregulated in these neurons when treated with theophylline. Cyclic AMP is involved in many physiological processes in cells, including cell growth. Discoveries like hers have the potential to significantly improve the quality of life for patients who experience breathing impairment after spinal cord injury by decreasing the likelihood that they will have to rely on a ventilator.
After completing her PhD, Kajana decided to move back to Toronto where she could continue researching the spinal cord while also having family support in raising her two children. She found a postdoctoral position at the Krembil Research Institute with Dr. Michael Fehlings, whose lab studies neuroprotective interventions after spinal cord injury. Here, Kajana worked with a different kind of spinal cord injury: a progressive, compressive injury called degenerative cervical myelopathy (DCM). DCM is common, occurring when the bones and ligaments of the spine slowly compress the spinal cord over time. This causes nerve damage and leads to numbness in the hands, back pain, and deficits in locomotive behaviors like walking.
Kajana noticed that DCM was curiously different from cervical spinal injury, which she had studied during her PhD: DCM did not affect breathing. Intrigued, she decided to dedicate the rest of her postdoc to figuring out why. Kajana developed a mouse model of DCM that had a similar symptom profile to humans. Importantly, as in humans, the mice had normal breathing. She hypothesized that the effect of spinal cord damage on breathing was related to whether that damage was acute or progressive. Perhaps the longer, more gradual time course of damage in DCM allowed a “backup system” to come online and protect breathing. Excitingly, this is exactly what she found. Specifically, a population of excitatory interneurons in the cervical spinal cord were sustaining breathing in DCM. To make sure these neurons were in fact the “backup system” and not essential for causing breathing, she used chemogenetic techniques to silence their activity in a population of healthy mice, and their breathing was unaffected, confirming her hypothesis.
The discovery of the cervical interneurons in her postdoc set the stage for Kajana’s research program as she built her own lab at the Medical College of Wisconsin. Her lab investigates the neural networks in the spinal cord responsible for crucial behaviors like breathing and walking. Her lab has explored how the cervical interneurons respond to breathing challenges like increased amounts of carbon dioxide or strenuous exercise. Kajana and her lab have also identified other neural pathways from the somatosensory cortex that connect to these cervical neurons and affect essential locomotor behaviors like walking. This connection was surprising because the somatosensory cortex is most often associated with the sensation of touch, and was not traditionally considered essential for motor behaviors. However, discovering this connection opened up an exciting window of opportunity to develop interventions for patients with injuries or diseases that affect their movement.
The interventions Kajana has explored so far focus on the connection between our sense of hearing and our ability to move. Because the somatosensory neurons in this pathway also interface with neurons in the auditory cortex, Kajana thought it was possible that sounds could directly affect movement. Kajana demonstrated that when mice listen to highly predictable music (like Mozart), this auditory-to-somatosensory-to-cervical pathway enables mice to walk more efficiently. Using calcium imagining, she was able to show that neurons in this pathway are active in response to the music. In addition to excitingly identifying 'dance neurons', this work also elucidated a potential mechanism for treatments like music therapy, which is effective for patients with Parkinson’s disease.
Kajana’s career researching the neural circuits in the brain and spinal cord is an exciting example of how basic research can directly influence how patients with spinal cord injuries and movement disorders are treated. Along the way, she also experienced challenges associated with the societal expectations of being a woman in an academic field. It was difficult for family and friends in her support system to understand the demands of an academic career (travel, time in lab, lack of structural support for motherhood). However, Kajana found that direct communication was always the best policy. Communicating with her PhD advisor about her plan to have children allowed her to efficiently plan her experiments around childcare. Communicating with her family about her career goals and the travel and time requirements of academia helped them support her through motherhood. And finally, being honest with herself about what she wanted was crucial: “It took me a long time to realize I really enjoy working as much as I enjoy being a mom,” she says. Kajana does both exceptionally well. And in an act of combining these loves, Kajana now enjoys performing East Indian classical dance on the weekends with her daughter, letting their ‘dance neurons’ bring them closer.
Find out more about Kajana and her lab’s research here.
Listen to Nancy’s full interview with Kajana on April 26, 2024 below!
