Paul Cullen, professor and director of graduate studies, is the recipient of the 2021-22 Distinguished Postdoctoral Mentor Award, which recognizes UB faculty members who excel in the mentoring of postdoctoral scholars. The award is bestowed on faculty members who not only teach their mentees, but also serve as an advocate, adviser and positive role model. Read the news story by Charles Anzalone.
By CHARLES ANZALONE
Published February 3, 2023
Paul Cullen, professor and director of graduate studies in the Department of Biological Sciences, is the recipient of the 2021-22 Distinguished Postdoctoral Mentor Award, which recognizes UB faculty members who excel in the mentoring of postdoctoral scholars.
The annual award, established in 2009, is presented by the Graduate School’s Office of Postdoctoral Scholars. It supports faculty members who not only teach their mentees, but also serve as an advocate, adviser and positive role model.
“The Office of Postdoctoral Scholars was thrilled at this year’s nomination pool,” says Kristen Ashare, director of the Office of Postdoctoral Scholars. “We are continuing to develop opportunities for highlighting mentorship and positive mentor-mentee relationship development here on campus.
“This annual award honors important work that otherwise goes unseen,” Ashare says. “I’m so grateful to Dr. Cullen and his dedication to mentorship that is recognized with this award.”
Cullen’s research investigates how cells sense changes in the environment and make decisions. He received his PhD from Washington University in St. Louis, where he studied nitrogen sensing and signaling in bacteria under Robert Kranz, professor of biology. Cullen was a postdoctoral fellow at the University of Oregon with George Sprague, now professor emeritus of biology, where he explored glucose signaling in the regulation of filamentous growth in yeast, primarily by mucin sensors and Mitogen-Activated Protein Kinase (MAPK) pathways. His interest in microbial signal transduction has continued as a faculty member in the UB Department of Biological Sciences for the past 18 years.
“All cells sense and respond to extracellular signals,” Cullen explains. “Sensing and relaying changes in the extracellular milieu is mediated by signal transduction pathways. One type of evolutionary conserved signaling pathway are Mitogen-Activated Protein Kinase (MAPK) pathways that can be controlled by G-proteins like the ubiquitous Cdc42. Cdc42-driven MAPK pathways are found in many eukaryotes and function in diverse ways to regulate cell differentiation, cell cycle progression and the response to stress,” he says. “We found a mucin-type protein that regulates MAPK pathways and are interested in learning about what these sticky molecules are sensing and how they trigger changes in cell shape.
“An interesting feature of MAPK pathways is that they can share components with other pathways in the cell,” Cullen notes. “How pathways that function in integrated networks induce the ‘right’ response is not well understood. Furthermore, inappropriate regulation of MAPK pathways can lead to cross talk, which is an underlying cause of diseases including cancers, immune diseases, inflammation and neurodegenerative disorders.”
Cullen’s nomination for the Distinguished Postdoc Mentor Award included a letter of endorsement from Beatriz Gonzalez, postdoctoral fellow in the Department of Biological Sciences.
“Dr. Cullen singlehandedly shaped my academic trajectory and is the main reason why I decided to stay in academia,” Gonzalez wrote in her nomination letter.
“During my experience as a graduate student, I had other advisers who did not drive my attention to an academic career. I was considering non-academic career choices until I met Dr. Cullen during an international collaboration, and I had the opportunity to spend 4 months in his laboratory.”
Gonzalez called her experience with Cullen “really fruitful in terms of research, writing and thinking.” As supervisor, Cullen “completely changed my vision about research and science,” she said.
“Dr. Cullen is a positive role model who has reinvigorated my love of science,” she wrote. “He really respects and understands my goals and makes a real effort to help me to achieve my aspirations. He also drives passion toward his research and transmits this passion to me.
“Dr. Cullen puts my career goals as a priority. It is not uncommon to hear from my postdoctoral colleagues that they are just cogs on a greater machine, their primary goal being achieving the PI’s goals,” Gonzalez wrote. “Rather, I feel that I am working on my future in Dr. Cullen’s laboratory and exploring exciting research together with my colleagues.
“In addition, as a woman, we are uniquely vulnerable and face more obstacles that other people in our same situation. I was so lucky to have one mentor like Dr. Cullen, who helps and supports me to keep fighting and pursue my dreams and goals against the odds.”
Gonzalez’s letter “impressed” the selection committee, Ashare said.
“It truly takes a mentor going above and beyond to close these leaks in the talent pipeline and we are so glad that Dr. Beatriz Gonzalez shared her story,” she said.
Signaling (MAPK) Pathways that Control Cell Polarity and Cell Differentiation
The CUllen Lab is interested in signal transduction pathways. All cells sense and respond to changes in the environment. Sensing and relaying changes in the extracellular milieu is mediated by signal transduction pathways. One type of evolutionary conserved signaling pathway are Mitogen-Activated Protein Kinase (MAPK) pathways. MAPK pathways are found in all eukaryotes and function in diverse ways to regulate cell differentiation, cell cycle progression, and the response to stress. An interesting feature of MAPK pathways is that they can share components with other pathways in the cell. How pathways that function in integrated networks induce the ‘right’ response is not well understood. Furthermore, inappropriate regulation of MAPK pathways can lead to improper signaling, which is an underlying cause of diseases including cancers, immune diseases, inflammation, and neurodegenerative disorders.
Our laboratory uses the model organism budding yeast to study MAPK pathways. In yeast, MAPK pathways control the response to stress and orchestrate cell differentiation to specialized cell types. Using this model, we have been able to identify new regulators of MAPK pathways and new mechanisms for their regulation. For example, we showed that mucins that regulate MAPK pathways in yeast undergo processing and release of an inhibitory extracellular glycodomain. More recently, we have identified an adaptor that regulates and might help to insulate the pathway (the pathway we study shares components with other MAPK pathways). We are currently working on how positional cues impact MAPK pathway signaling through the Rho GTPase Cdc42.
The specific MAPK that we study in our laboratory regulates a cell differentiation response called filamentous growth. Filamentous growth is a fungal-specific growth mode that occurs in yeast and many other fungal species. During filamentous growth, cells change their shape and grow as branched filaments. In some species of pathogenic microorganisms, filamentous growth is required for virulence. Among the signaling pathways that regulate filamentous growth is an ERK-type MAPK pathway called the filamentous growth (fMAPK) pathway. Studying how MAPK pathways regulate filamentous growth in yeast can shine light on MAPK-dependent differentiation responses in general as well as the molecular basis of fungal pathogenesis.
The proteins that regulate the fMAPK pathway in yeast have been identified by our laboratory and other laboratories. A signalling mucin-type glycoprotein (Msb2), together with polar landmarks, regulates the cell’s major polarity GTPase Cdc42p, which activates a canonical p21-MAPKKK-MAPKK-MAPK kinase cascade. Key questions surrounding the regulation of the fMAPK pathway remain unaddressed. One question is how does the mucin Msb2 regulate the GTPase module? A second question is how is a specific signal sent by a pathway that shares components with other MAPK pathways in the cell? Our lab is approaching these questions in different ways:
1. By the development and utilization of genomic and proteomic approaches, we have discovered and are continuing to identify proteins that regulate the filamentous growth pathway. For example, we used the fact that the extracellular domain of Msb2 is shed to develop a high throughput screening approach called secretion profiling to identify new regulators of Msb2/fMAPK.
2. By building new assays to measure and quantitate filamentous growth, we are learning more about the molecular basis of the response. We are currently utilizing genetics, microscopy, and bioinformatics analysis to define aspects of filamentous growth regulation.
3. Biochemistry, molecular biology, and in vivo protein-interaction approaches (e.g. two-hybrid analysis and FRET) are being employed, which are critical to determine how proteins that regulate MAPK pathways function to induce a response.