Alex Minella, MD, assistant professor in medicine, is a Midwest native, but lived on each coast before settling in Chicago. He was an undergraduate at Yale and a medical student at Vanderbilt before moving to Seattle for clinical and postdoctoral training. He came to Feinberg in 2007 and, in addition, to running a research laboratory, is a practicing oncologist. His clinical activities currently focus exclusively on the care of inpatients at Northwestern Memorial Hospital.
Minella lives downtown with his family, which he says allows him to take advantage of the city’s museums and local music venues. As a student, Minella played the trumpet, and while he no longer has the free time to play, he still enjoys visiting record shops to search for old jazz albums from his childhood. He also is a lifelong baseball fan and tries to see the White Sox at least a few times a year.
What brought you to the Feinberg School of Medicine?
First and foremost, Northwestern seemed to me to be one of a few institutions that vigorously supports physician-scientists as laboratory investigators. This career model seems to be increasingly under threat. Being able to focus on basic research while also having the privilege to care for patients, I am engaged in what I always thought was the most compelling career. So it was critical to me that I work at an institution that valued the path my life’s work has taken.
Also, at the time that I was finishing my postdoctoral work, which was focused initially on studying the regulation of one member of a class of cell cycle proteins called cyclins, I was becoming more interested in cell cycle control within hematopoietic stem cells and during hematopoietic cell maturation. In 2006 and 2007, before I moved here, Jonathan Licht, MD, chief of the Division of Hematology-Oncology, was recruiting a number of laboratory investigators to build on existing strengths here at Northwestern in the study of hematologic malignancies. I thought that there was a real opportunity for me to develop both an independent research program during a time of exciting, departmental growth and to learn new skills in the study of hematopoiesis from my colleagues-to-be in the division.
What are your research interests?
The molecular circuitry that regulates cell proliferation is at the center of all the work we do in my lab. Ultimately, cancer is a disease of inappropriate cell division. My research has increasingly focused on understanding precisely how cell cycle regulatory networks are integrated with the broader biology of the cell. For example, we are submitting a paper shortly describing how inappropriate expression of a key regulator of entry into S-phase entry (when the cell replicates its DNA) causes activation of hypoxia signaling within breast epithelial cells. This work, which is led by Tanushri Sengupta, a postdoctoral fellow in my lab, has led us to hypothesize that hypoxia signaling, which is thought to promote the survival and spread of cancer cells, can be co-opted by these cell cycle regulators when they are aberrantly expressed.
In other work led by Yanfei Xu, another postdoctoral fellow in my lab, and Ka Tat Siu, a graduate student, we have focused on DNA damage signals that are generated in response to defective cell cycle controls in hematopoietic cells. We believe these signals are at the heart of abnormalities we have identified in blood cell maturation and stem cell function of mice we have engineered to model several of the defects in cell cycle control that occur in human cancers. We hypothesize that defective cell cycle controls and the cellular responses to these may contribute to the pathogenesis of blood diseases in humans, such as myelodysplastic syndromes and leukemia.
What is the ultimate goal of your research?
As a result of my training, the research that we perform focuses on solving and studying particular molecular mechanisms in physiologically relevant systems rather than a specific disease-centered approach. However, as an oncologist, I am obviously interested in having a measurable impact upon the diagnosis and treatment of cancer. It is my hope that our work will ultimately illuminate steps in the development of cancer that lend themselves to new therapies or diagnostic approaches. Whether it is us or other groups that develop these practical applications is less important to me than that our work makes substantive contributions to understanding the molecular bases of cancer development and progression.
How does your research advance medical science and knowledge?
Most cancer researchers believe that the great challenges that remain in improving diagnostics and treatments will take both advances in fundamental science as well as high-quality translational research and well-designed clinical trials. In my lab, our efforts focus largely on fundamental cancer biology.
What types of collaborations are you engaged in across campus (and beyond)?
We have just started a project with Jane Winter, MD, a lymphoma specialist in our division, in which we are studying the role of a particular cell cycle inhibitory protein in potentially regulating the response of diffuse large B-cell lymphomas to a commonly used therapy, rituximab. I have been collaborating with Ming Zhang, PhD, in the study of this same cell cycle inhibitor, p21, and its role in regulating breast tumor progression. Also, for about two years, we have been collaborating with Marsha Rosner, PhD at the University of Chicago in the use of computational modeling and live cell imaging to develop an integrative approach to studying key steps involved in the early stages of cell cycle progression, leading to DNA replication.
How did you become interested in this area of research?
I started in the cell cycle field working as a summer student in Tom Kelly, MD, PhD’s lab at Johns Hopkins. There, I was working on yeast cell cycle proteins, including one protein with an unknown function at the time, but later was found to be critically important for the initiation of DNA replication and then was discovered to interact with the proteins I have been working on since my postdoctoral work. The striking evolutionary conservation of cell cycle regulatory proteins from single cell organisms to humans as well as their fundamental role in tumor biology is what originally drew me to the field. The cell cycle is at the nexus of fundamental biology and the molecular basis of cancer, and there are many questions remaining, including whether specific cell cycle regulatory mechanisms are molecular linchpins for tumor cell proliferation and survival, and, if so, in which cancers?
How is your research funded?
The National Institutes of Health provides our chief source of funding – currently in the form of a K-grant awarded in 2007 to support my transition from mentored to independent research and a 2010 R01 award that supports our work in studying cell cycle regulation in hematopoiesis. The collaborative projects I described are supported by the Chicago Biomedical Consortium (Searle Funds) and a Schwartz Family Lymphoma Research award. I am especially grateful for a number of new investigator awards I have received from several organizations and foundations, including an American Society of Hematology Scholar Award, American Cancer Society institutional research grant, Leukemia Research Foundation New Investigator Award, Schweppe Foundation New Investigator Award, and Translational Scholar Award from the Sidney Kimmel Foundation for Cancer Research.