Throughout my training, I have been fortunate enough to be in well-funded laboratories that enabled me to focus of answering key scientific questions on how stem cells were regulated in normal and disease states. As I started my own research laboratory in 2012, I faced the exciting possibility that lay ahead of me with an empty lab and numerous ideas on how insights into stem cell biology could be used to develop more effective cancer therapies. As I began recruiting staff, it soon became apparent that the success and longevity of the lab were directly linked to our ability to gain funding to support our efforts. The stark reality of funding difficulties soon sunk in and I quickly realized that I was entering a delicate cycle in which one needs money to fund the lab to generate exciting findings and these findings subsequently generate additional funding which supports the lab. Seed money from the Ohio Cancer Research Associates (OCRA) empowered my laboratory to conduct the key studies that have laid the foundation for many projects that have since been funded by National Institutes of Health grants (K99/R00 Pathway to Independence Award, R01 and R21 research grants), the Sontag Foundation, Cleveland Clinic Product Development Fund, V Foundation for Cancer Research, Voices Against Brain Cancer, and an American Cancer Society Institutional Research Grant to the Case Comprehensive Cancer Center and provided the laboratory financial stability to enable us to aggressive develop therapies against cancer stem cell in malignant brain tumors and breast cancer.
The goal of my laboratory is to understand how stem cell programs work in tumors to drive growth and therapeutic resistance. We have a particular interest in how cells with enhanced stem cell programs (also called cancer stem cells) interact with the surrounding microenvironment as this is a key regulatory process and offers a novel area for therapeutic development. We previously observed that cancer stem cells in malignant brain tumors associated with blood vessels and had some ideas as to how a bidirectional relationship between the cancer stem cells and blood vessels was regulated. The seed funding from OCRA allowed us to test this idea and we identified a signaling system that was used by cancer stem cells to interact with blood vessels. At the same time, a biotech company in California was developing inhibitors against this pathway and we were able to collaborate with them to show the efficacy of targeting the interaction between cancer stem cells and the blood vessels. This work has recently been published and the biotech company is aggressively pursuing clinical trials with these inhibitors. This success story highlights the power of scientific collaboration but could not have been possible without the seed funding from OCRA. After identifying this signaling system, we expanded our findings to evaluate how cancer stem cells directly communicate with one another and we now have active projects in this area in malignant brain tumors, breast cancer, prostate cancer, and leukemia.
Cancer impacts us all, 1 in 2 men and 1 in 3 women will develop cancer at some point in their lifetime. For advanced cancers, such as malignant brain tumors, prognosis remains dismal and the 5-year survival rate remains around 3% and this has not changed in the last 30 years. These statistics are daunting and underscore the need for more effective therapies. We are at the beginning of a scientific revolution and now have the capacity to use cutting edge methods to understand the genetics and behavior of each tumor down to the single cell level and evaluate multiple drug combinations. More effective therapies are on the horizon. However, obtaining funding to pursue ideas that will lead to these more effective therapies remains challenging. This is where foundations like OCRA that provide seed money can make a big difference. Receiving OCRA seed money at a critical time in the establishment of my laboratory ensured we could pursue our ideas, attain financial stability to continue our work, and generate results that could be translated one step closer to patients. There are many young scientists in a similar position that could greatly benefit from support at the early stages in their career. Empowering OCRA to support projects with seed money is not only an investment in the future but an assurance that cancer patients have access to more effective therapies. Thank you for your generosity.
Dr. Justin Lathia leads a translational cancer stem cell research laboratory and Assistant Professor in the Department of Cellular and Molecular Medicine at the Lerner Research Institute, part of the Cleveland Clinic. He is also an Assistant Professor of Molecular Medicine at the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University and is a Member of the Case Comprehensive Cancer Center. Dr. Lathia is also an Adjunct Faculty Member in the Department of Biological, Geological, and Environmental Sciences at Cleveland State University.
Dr. Lathia was born and raised in Central Pennsylvania and received a B.S. and M.S. from Drexel University in Philadelphia, PA in 2003. While at Drexel, he developed targeted ultrasound contrast agents which preferentially bound to newly formed vessel in breast cancer models under the guidance of Dr. Margaret Wheatley. As part of the NIH-Cambridge Graduate Partnership Program, Dr. Lathia completed his doctoral dissertation at both the National Institutes of Health and Cambridge University in the U.K. with Drs. Mark Mattson, Mahendra Rao, and Charles ffrench-Constant. His worked focused on the role of cell adhesion molecules during the development of the nervous system. After completing his Ph.D. in 2008 he completed post-doctoral fellowships at Duke and the Cleveland Clinic with Dr. Jeremy Rich where he focused on the role of cell adhesion in regulating cancer stem cells in brain tumors. In 2012, Dr. Lathia moved to the Department of Cellular and Molecular Medicine as an independent investigator and the work in his lab focuses on how the stem cell state is regulated in advanced cancers. Projects in the Lathia lab involve understanding how cancer stem cells interact with their surrounding microenvironment as well as one another with the goal of identifying unique pathways for therapeutic development.
Dr. Lathia has co-authored over 80 publications and work in his lab is currently supported by multiple National Institutes of Health grants (K99/R00 Pathway to Independence Award, R01 and R21 research grants), the Sontag Foundation, Cleveland Clinic Product Development Fund, and Lerner Research Institute. His lab has previously received funding from the Ohio Cancer Research Associates, V Foundation for Cancer Research in the form of a V Scholar Award, Voices Against Brain Cancer, and an American Cancer Society Institutional Research Grant to the Case Comprehensive Cancer Center. Dr. Lathia also contributes as a peer reviewer to over 50 journals, has served on multiple grant review panels for the National Institutes of Health and private foundations such as the Maryland Stem Cell Foundation, and recently served as a co-organizer for the inaugural cancer stem cell meeting held in Cleveland in August 2014, which drew over 300 attendees from over 25 states and 15 countries.
He resides in Shaker Heights with his wife Amanda and their 3 year-old son Alexander and 7 month-old daughter Anjali.
In 1993, I was among the first researchers at the University of Cincinnati to receive funding from the Ohio Cancer Research Associates. At that time, I was an Assistant Professor in Dermatology, trying to establish my independent path in research. This seed money enabled me to set the foundations for research that started as an idea that was both promising and controversial. This funding allowed me to determine the role of the melanocortins alpha-melanocyte stimulating hormone (alpha-MSH) and ACTH in human pigmentation. My laboratory provided evidence that alpha-MSH and ACTH stimulate the synthesis of the pigment melanin in cultured human pigment cells, the melanocytes, by activating a specific receptor termed the melanocortin 1 receptor (MC1R). Given the importance of skin pigmentation in the response of the skin to sun exposure and the risk for skin cancer, I investigated the role of melanocrotins in the response of human melanocytes to ultraviolet radiation (UV), the damaging radiation from the sun that causes skin cancer. The seed money from the Ohio Cancer Research Associates allowed me to generate sufficient data that won me my first four-year grant from NIH.
In 1997, I was awarded for the second time seed money from OCRA. This time, I began investigating the effects of different forms or alleles of the MC1R gene on the susceptibility of different individuals to melanoma, the most deadly form of skin cancer. Expression of some forms of the MC1R gene results in red hair, fair skin, poor tanning ability, and increased risk for melanoma. Using cultured melanocytes from different donors, we started to correlate the donor’s MC1R alleles with his/her response to melanocortins and UV. We found that the same forms of the MC1R gene that cause red hair, result in loss of function of the receptor, and render melanocytes very sensitive to the damaging effects of UV, which explains the increased susceptibility to melanoma. This funding from OCRA made it possible for me to obtain a second NIH-funded grant for five years.
I was also funded by OCRA in 2001 for a third time. The seed money that I received from them over the years promoted my career and allowed me to train a considerable number of students and postdoctoral trainees. Interestingly, a colleague in my department whom I trained as a postdoctoral fellow is currently funded by OCRA. The basic research in my laboratory that was first supported by OCRA is entering the translational phase. The knowledge gained about the melanocortins and the MC1R and their effects on human melanocytes led us to design and synthesize peptides based on the chemical structure of alpha-MSH that not only increase pigment synthesis by the melanocytes, but also repair sun-induced DNA damage that causes skin cancer. Our goal is to develop these peptides for topical application that would prevent sun-induced skin cancer. This project has just been funded for four years by a grant from the National Cancer Institute. The outcome of this project is expected to have a tremendous impact on the prevention of skin cancer, the most prevalent type of all human cancers.
The journey that began thirteen years ago would not have reached its current destination has it not been fueled by seed money from OCRA. This is a testimony for how giving a new idea a chance have led to discoveries that ultimately will prevent skin cancer, mainly melanoma, one of the most challenging types of human cancers.
How the OCRA grant helped my career. Shortly after my lab opened doors in 2007, I applied for the pilot grant from Ohio Cancer Research Associates. It was the first time I seriously wrote a grant proposal and the writing process itself taught me a lot. It was a purely joyful moment when I received the notice in early 2008 that my proposal was funded. The OCRA grant certainly played an important role for providing seed money for us to generate preliminary data and secure federal funding later, but it did more than that. It boosted the confidence of a new investigator, and it helped a new investigator to establish track record for applying to other funding sources. I am also grateful that the comments from expert reviewers helped set priorities in my project development. The OCRA grant really sowed the seed of success for me to acquire 1.8 million federal funding since I joined UT. Last but not least, the active research program in my lab, first funded by the OCRA grant, allowed me to give over 30 undergraduate, graduate and postdoctoral researchers hands-on training and helped engage my students in the classroom with cutting-edge research progress.
Song-Tao Liu, Ph.D. is currently Associate Professor at Department of Biological Sciences, University of Toledo. He obtained his Bachelor degree in 1990 from Wuhan University in China majoring in biochemistry. After a stint in the first Sino-American joint venture in biotechnology as a product scientist, he went on to pursue his Ph.D. studies in Shanghai Institute of Biochemistry, Chinese Academy of Sciences. He graduated in 1997 with award-winning research on transcriptional regulation of genes involved in the symbiosis between rhizobial bacteria and leguminous plants. Partially influenced by the loss of two grandparents from colon cancer and breast cancer, he decided in 1998 to move to Fox Chase Cancer Center in Philadelphia to work as a postdoctoral fellow. He has since been active in the area of basic cancer research. Dr. Liu joined the University of Toledo in 2007 and got his first external funding from Ohio Cancer Research Associates in 2008. After winning the pilot grant from Ohio Cancer Research Associates, his work at UT has been funded by National Science Foundation and National Cancer Institute. The research theme in his lab is on the relationship between chromosomal instability and cancer development. The ever-changing chromosome make-up in cancer cells affords them the ability to proliferate, metastasize and develop drug resistance. Dr. Liu’s work probes the defects underlying chromosomal instability and explores ways to rein in the malignant property of cancer cells for cancer prevention and treatment. His work has attracted collaborations with other scientists including Nobel laureate Avram Hershko. He was also the recipient of the Award for Excellence in Research in 2014 at the College of Natural Sciences and Mathematics of UT.
Dr. Denis Guttridge is a Professor in the Department of Molecular Virology, Immunology, and Medical Genetics at The Ohio State University. He received his Bachelors of Science degree from the University of California, San Diego, where he majored in Cell Biology and Biochemistry. After receiving a Master’s Degree in Biochemistry from Long Beach State University, he obtained his Ph.D. in Biological Sciences from the University of California, Irvine, and subsequently performed postdoctoral training at the Lineberger Cancer Center at the University of North Carolina, Chapel Hill in the laboratory of Dr. Albert S. Baldwin. As a postdoctoral fellow, Dr. Guttridge performed studies to examine the role of a transcription factor called NF-kB (pronounced NF-kappaB for nuclear factor kappa B) in regulating the differentiation of cells. Since differentiation is a process that is often compromised in cancer, the idea was to study how NF-kB controls differentiation as a way to better understand the role of this transcription factor in cancer.
To study differentiation, Dr. Guttridge utilized a model of skeletal muscle. Muscle cells readily differentiate and are amendable to both in vitro and in vivo studies. As a postdoc fellow, Dr. Guttridge made the discovery that NF-kB inhibits skeletal myogenesis, and that in response to cytokines such as TNFa, muscle turnover occurs via NF-kB. He also made the link that this regulation may occur in a muscle wasting condition that often occurs in cancer patients, especially in pancreatic cancer, called cachexia. This syndrome is defined by rapid weight loss due to skeletal muscle wasting, and patients that suffer from cachexia are much more difficult to treat with standard care. As a result, cachexia patients have a poorer prognosis and a lower quality of life.
Dr. Guttridge has continued working on cachexia in his own laboratory at The Ohio State Comprehensive Cancer Center (CCC) and now serves as director of a cancer cachexia program within the CCC at OSU. In his own lab, he focuses on further understanding the mechanisms by which NF-kB functions in skeletal differentiation that may be applicable to cancer and cachexia, and also is investigating other mechanisms leading to muscle loss in pancreatic cancer patients.
Outside OSU, Dr. Guttridge serves as a standing member of a National Institutes of Health review committee for grant funding. He has also participated as a reviewer for an NIH National Institute of Neurological Disorders and Stroke special emphasis panel on rare muscle diseases, as well as for the Department of Defense Breast Cancer Program. He also served an ad hoc reviewer for scientific journals, and was a recipient of an Ohio Cancer Research Associates award, which was instrumental in getting his laboratory off the ground as a new faculty member. He currently leads projects funded by the NIH National Cancer Institute, the National institutes of Arthritis and Musculoskeletal and Skin and National Institute of Neurological Disorders and Stroke.