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Working at the Tip of the Iceberg in Neurodevelopment




Kimberly Mulligan 

(CSU Sacramento, 2015 & 2016 New Investigator) is a developmental biologist working to identify environmental factors that may increase the risk of onset or increase the severity of neurodevelopmental disorders, like autism and Fragile X syndrome. 

When asked about her motivation to work in this field, she has a very personal answer: "That a single cell can give rise to hundreds of specialized cell types within an organism composed of billions and trillions of cells is just incredible to me—and the more I know, the more amazed I become. I was in the developmental biology graduate program at Stanford University when my best friend and roommate, who was in the same graduate program, took her own life as a result of her tremendous struggles with bipolar disorder. Part of my grief involved poring over the literature on neuropsychiatric disorders in an effort to try to understand how this happened to my dear friend. This ultimately led me to study molecular neurodevelopment and neuropsychiatry as a postdoctoral fellow under Ben Cheyette at [University of California San Francisco, UCSF]."

"The complexity of neurodevelopmental and neuropsychiatric disorders is stunning, and we are just hitting the tip of the iceberg in terms of understanding their molecular underpinnings. That is why there is such a deficit of effective treatments. Take autism alone—hundreds of genes and thousands of genetic variants have been linked to autism, and these genetic variants often only cause autism when found in combination with other variants. And now we understand that environmental factors (like maternal autoantibodies, drugs, environmental chemicals) can influence the epigenetics of the developing fetus to confer risk of neurodevelopmental impairment. Complete understanding of the causes of neurodevelopmental and neuropsychiatric disorders will require a monumental effort in the field—it is a cause that is precious to me, and I am dedicated to doing what I can to help move the field forward." 

Dr. Mulligan says the "CSUPERB New Investigator Award I received in 2016 was critical for launching my research program. It allowed me to pay a number of undergrads for their research efforts over the summer. [It] was also my first experience with 'grant management,' so there were certainly bumps along the way! For example, we have different people in different offices that manage various aspects of grants, and it was the CSUPERB grant that allowed me to learn the ropes… I now have an appreciation for the pace of research at teaching universities…I have come to view my research as an extension of my teaching—it is providing students with experiential learning opportunities at the bench. Whether data generation is slow or fast, my students are gaining a fabulous skill set. That is the win for me."

In fact, Dr. Mulligan has trained a remarkable number of undergraduates in her lab already. She says, "Managing a lab of 20-25 students [primarily undergraduates] has certainly provided a steep learning curve! I think the most valuable lesson I've learned is the importance of letting students fail and encouraging them to do their own troubleshooting. Of course, this usually means that research moves at a snail's pace, but it also means that students more effectively learn how to think critically and have a greater sense of scientific ownership over their projects. During weekly lab meetings I expect to see their data and I ask questions intended to keep them on the right track, but I intentionally stray away from hand-holding—I've learned that [it] does not serve them well in the long-run. Struggle and challenge provides students with opportunities for growth. My growth has been learning to have the patience to allow students to struggle at the bench, which is much easier said than done."

The students supported by the CSUPERB grant are already moving on to the next phases of their education and careers at universities including Georgetown University, UC Davis, Ross University, and University of Nevada Las Vegas. Other students have won additional support for their research activities from the CSU Sacramento RISE program and the Stem Cell Masters Program. 

She concludes, "There is so much that makes me happy about my decision to come to CSU Sacramento. Just after earning my PhD, I was presented with the opportunity to teach a developmental biology class at San Francisco State University (SFSU). Carmen Domingo at SFSU gave me complete academic freedom with my course—which was frightening, exhilarating, challenging….and so tangibly fulfilling. I have always loved research and always will. But the impact factor of teaching—the sheer number of lives that you can potentially affect—is incredible to me. Being in my hometown, teaching at Sac State, getting to contribute to the community in which I was raised feels like a dream. I am especially proud of the diversity in Sacramento, which is reflected on our campus. I am a fierce advocate for diversity in science—and being at Sac State puts me in the wonderful position of training diverse students and helping to launch them into careers in the biomedical workforce…"

"The two biggest qualities I look for in research students are curiosity and kindness. Students who are curious tend to be the most intrinsically motived at the bench. Kindness is the other big requisite. I realized early on that I was fostering a community in my lab—and I want that community to be a safe, supportive space for all of my students. Especially for my students who come from underrepresented or marginalized backgrounds and are often particularly vulnerable—I want my lab to be a place that is inspiring and motivating, which means there is no space for arrogant, belittling, or other versions of unkind people."



Captions for photos (below, left to right):

1. Drosophila Neural Stem Cells. The Mulligan lab is interested in examining how the combination of genes and environment converge to affect neural stem cell proliferation. Type I and II neuroblasts (Drosophila neural stem cells) are distinguished using anti-Prospero (red), anti-Deadpan (green), and DAPI (blue). Photo credit: Chloe Welch, Jacqueline Stein and Lillian Murphy.

2. Synapse formation at the larval neuromuscular junction. A common phenotype of neurodevelopmental disorders involves changes in synapse formation. The Mulligan lab can count synaptic boutons (marked in green using anti-Discs large) and quantify how environmental exposures influence the number of boutons formed. The neuronal membrane is marked in red using Cy3-conjugated anti-Horse Radish Peroxidase. Photo credit: To Hien Doan, Angelina Tupikova, Ashlie Lopez and Rafael Corona.

3. Axon outgrowth in the adult Drosophila brainAnti-FascillinII (green) marks axons in the mushroom body (MB), and adult neural structure required for olfactory-based learning and memory. A number of autism associated genes that are functionally conserved in Drosophila (fruit flies) cause axon outgrowth defects in this structure, thus the Mulligan lab examines how environmental exposures converge with autism risk genes to disrupt axon outgrowth in the MB. Photo credit: Lillian Murphy, Kimberly Nguyen, and Brandon Stryder.

4. The Courtship AssayThree courtship behaviors are shown (following, wing extension, and copulation). The courtship assay quantifies six stereotyped innate courtship behaviors of fruit flies, and provides a functional assay to measure how genes and environment interact to potentially impair the neurodevelopmental program. Photo credit: Lillian Murphy


This story is one in a series of PI profiles published in concert with the AY 17-18 CSUPERB Annual Report. Read the report here and find other profiles here.