Office: BMSB 939A
Phone: (405) 271-2227 ext. 61233
Fax: (405) 271-3092
Biochemistry & Molecular Biology
PhD, SUNY at Stony Brook, 1981
PhD, SUNY at Stony Brook, 1981
Serum mass profiling for early detection and monitoring of cancer: We are developing a disease detection/monitoring technology we denote as serum mass profiling. This liquid mass spectrometry technology is based on the hypothesis that all organs and tissues are constantly sloughing off peptides and other biomolecules into the peripheral blood and that the patterns or profiles of these molecules reflect the physiological state of the organism. In this way, it is hypothesized that all disease states will have a unique pattern of such molecules in the sera of affected individuals. We are using this technology for early detection of a variety of cancers including those of the lung, pancreas, esophagus, ovary, breast, and endometrium. The earlier cancers can be detected the greater success of treatments. We especially envision this technology being useful for high risk groups for these cancers, e.g., tobacco smokers and lung cancer and pancreatitis patients and pancreatic cancer. In addition, the tandem mass spectrometry capabilities of modern mass spectrometry instruments make the identification of disease discriminating biomolecules possible. Such identifications result in additional mechanistic information about disease processes, identification of novel biomarkers, and provide targets for future therapeutic interventions.
Developing serum profiling technology for screening and monitoring individuals with traumatic brain injury (TBI): TBI is the signature injury of the United States Operation Iraqi Freedom and Operation Enduring Freedom (OIF/OEF) campaigns in the Middle East. TBI produces long term effects (termed persistent postconcussion syndrome-PCS) in sizeable numbers of deployed veterans over time. We propose to develop straight-forward, non-invasive, inexpensive, and robust technology for analyzing and monitoring TBI and related PCS symptoms, utilizing screening of serum for correlative biomarker changes at the molecular level. We will employ high-resolution and high-accuracy electrospray ionization (ESI) mass spectrometry (MS) for profiling/”fingerprinting” veteran sera for TBI-specific changes. This study is based on the hypothesis that organs and tissues are shedding/secreting a wide variety of biomolecules into the peripheral blood, and that these processes are regulated by and dependent upon physiological and pathological changes. Such processes are hypothesized to stem from systemic and homeostatic stress and defense mechanisms plus direct inputs from diseased tissues. Thus each unique disease state is hypothesized to have a unique serum biomolecule mass profile which will change in unique ways with disease progression or amelioration. Our laboratory is providing evidence for this serum mass profiling hypothesis by demonstrating the effectiveness of our liquid mass spectrometry technology to detect very early stages of different cancers in patients using very small blood samples. We anticipate having equal success analyzing TBI and PCS in veterans as well.
Early detection and monitoring of Alzheimer’s disease (AD), diabetes, and cardiovascular disease: We are applying our novel serum mass profiling technology to develop straight-forward, accurate, robust, and inexpensive blood tests for the early detection and monitoring of diseases that affect large numbers of individuals in the United States and internationally. These include Alzheimer’s disease and other dementias, diabetes, and cardiovascular disease. All these diseases have prominent roles in patient care. We believe our disease monitoring blood tests can make significant contributions to their amelioration through improved early detection, monitoring, and development of therapeutic interventions.
Serum mass profiling for monitoring bacterial infections and other human pathogens: Serum mass profiling is being used to distinguish rodents infected with wild-type or mutant bacteria, e.g. Listeria monocytogenes, from non-infected control mice. Performing these mass spectrometry (MS) studies on serum using such rodent models of bacterial infection and human studies will yield clues about mechanisms of pathogenicity and host responses to important human pathogens. With respect to human studies, we are identifying novel circulating biomarkers that could be used as valid diagnostic tools for neurocysticercosis (NCC)-associated epilepsy, and to help us better understand the natural history of NCC. MS serum profiling information will be useful for identification of biomarkers specific different bacterial and human pathogen infections, and will aid in diagnosis, following disease progression, and the design of novel therapeutic interventions.
Understanding zinc protein-mediated cellular events: Present studies are focused on studying the largest superfamily of eukaryotic transcription factors, zinc finger proteins containing DNA and RNA binding domains which coordinate zinc ions. We are studying how the prototypical zinc finger proteins transcription factor IIIA and Sp1, as well as other zinc finger proteins, bind metal ions and redox molecules, interact with inhibitors, and interact with nucleic acids, and other proteins. We are elucidating these mechanisms through the use of DNA binding and transcription assays, in vitro mutagenesis, mass spectrometry analysis, two-hybrid assays, chromatin immunoprecipitation (CHiP) assays, and immunohistochemistry of tissues. Such studies will lead to better understanding the mechanisms of protein-nucleic acid and protein-protein interactions among members of this superfamily of proteins, numbering over a thousand in vertebrates. Understanding of these interactions at the molecular level will aid in the design of therapeutics to ameliorate diseases at the transcriptional level. These studies have implications for understanding how cells regulate zinc and zinc protein levels (zinc homeostasis), and for drug design involving zinc proteins in HIV and metalloproteinases.
Research Collaborations: I am actively collaborating on research projects with a number of clinically oriented groups on campus. These include the Surgery Department (Drs. Postier, Deb, Burkhart, Li, Thompson, Reinersman, Ms. Megan Lerner) of which I am an Adjunct Professor (25 year relationship), the VA and OUHSC Neurology Department (Dr. James Couch, 4 year relationship, Dr. Calin Prodan, 5 year relationship), College of Public Health (Dept. of Biostatistics, Dr. Helene Carabin, Dr. Michael Anderson, 5 year relationship), Department of Medicine (Dr. Doug Drevets, 8 year relationship, Dr. Courtney Houchen, 7 year relationship), Dean McGee Eye institute (Dr. Robert Leonard, 3 year relationship, was a medical student intern in my lab in 1991, Dr. Brian Firestone, 1 year relationship), OB/GYN Department (Dr. Doris Benbrook Scott McMeekin, and Dr. Joan Walker, 10 year relationship), OUHSC Department of Neurology (Dr. Linda Hershey, 3 year relationship, Mr. Paul Tompkins, 20 year relationship), Department of Urology (Dr. Kelly Stratton, 1 year relationship), Department of Pediatrics (Dr. Dharambir Sanghera, 3 year relationship), Harold Hamm Diabetes Center (Dr. Tim Lyons-now at Queen’s University, Belfast, 5 year relationship), Department of Psychiatry & Behavioral Sciences (Dr. Larry Gonzalez, 8 year relationship), OMRF (Dr. Rheal Towner, 4 year relationship). Off campus I am collaborating on clinical projects with Dr. Stephen Dubinett at the UCLA Medical Center (4 year relationship), and Vedentam Rajshekhar and Prabhakaran Vasudevan at the Christian Medical College, Vellore (5 year relationship). Entrepreneurial collaborations include Advion in Ithaca New York (a mass spectrometry company, Dr. Nigel Sousou and Dr. Simon Prosser, 2 year relationship) and Analytical Research Laboratories (ARL, a bioanalytical company), Oklahoma City (Dr. Tom Kupiec and Dr. Nicole Vu, 15 year relationship).
- Hocker JR, Debb SJ, Li M, Lerner MR, Lightfoot SA, Quillet AA , Hanas RJ, Reinersman M, Thompson JL, Vu NT, Kupiec TC, Brackett DJ, Peyton MD, Dubinett SM, Burkhart HM, Postier RG, Hanas JS. (2017) Serum Monitoring and Phenotype Identification of Stage I Non-Small Cell Lung Cancer Patients. Cancer Investigation 85: 573-585.
- Prabhakaran V, Drevets DA, Ramajayam G, Oommen A, Babu JJ, Anderson MP, Hanas JS, Rajshekhar V, Carabin H. (2017). Comparison of Monocyte Gene Expression among Patients with Neurocysticercosis-Associated Epilepsy, Idiopathic Epilepsy and Idiopathic Headaches in India. PLoS Neglected Tropical Diseases, PNTD-D-17-00113R1 - EMID:86f92aef89d70c43.
- Qu D, Johnson J, Chandrakesan P, Weygant N, May R, Aiello N, Rhim A, Zhao L, Zheng W, Lightfoot S, Pant S, Irvan J, Postier R, Hocker J, Hanas J, Ali N, Sureban S, An G, Schlosser M, Stanger B, Houchen CW. (2015) Doublecortin-like kinase 1 is elevated serologically in pancreatic ductal adenocarcinoma and widely expressed on circulating tumor cells. PLoS ONE, 10:e011893
- Hocker JR, Postier RG, Li M, Lerner MR, Lightfoot SA, Peyton MD, Deb SJ, Baker CM, Williams TL, Hanas RJ, Stowell DE, Lander TJ, Brackett DJ, Hanas JS. (2015) Discriminating patients with early-stage pancreatic cancer or chronic pancreatitis using serum electrospray mass profiling. Cancer Letters 359:314-24.
- Hanas JS, Peyton MD, Lerner MR, Lightfoot SA, Deb SJ, Hanas RJ, Vu NT, Kupiec TC, Stowell DE, Brackett DJ, Hocker JR. (2014) Distinguishing Patients with Stage I Lung Cancer versus Control Individuals using Serum Mass Profiling. Cancer Investigation, 32:136-143.
- Hocker JR, Mohammed A, Aston C, Brewer M, Lightfoot SA, Rao CV, Hanas JS. (2013) Mass Profiling of Serum to Distinguish Mice with Pancreatic Cancer Induced by a Transgenic Kras Mutation. Intern. J. Cancer. 133:2662-71.
- Hocker JR, Drevets DA, Dillon MJ, Hanas JS. (2012) Discriminating experimental Listeria monocytogenes infections in mice using serum profiling. Appl Microbiol Biotechnol 96:1049-58.
- Hocker JR, Peyton MD, Lerner MR, Lightfoot SA, Hanas RJ, Brackett DJ, Hanas JS. (2012) Distinguishing non-small cell lung adenocarcinoma patients from squamous cell carcinoma patients and from control individuals using serum profiling. Cancer Investigation 30:180-8.
- Hocker JR, Bishop EA, Lightfoot SA, Lerner MR, Peyton MD, Brackett DJ, Hanas RJ, McMeekin DS, Walker JL, Hanas JS. (2012) Serum profiling to distinguish early-stage and late-stage ovarian cancer patients from disease-free individuals. Cancer Investigation, 30:189-97.
- Hocker JR, Peyton MD, Lerner MR, Mitchell SL, Lightfoot SA, Lander TJ, Bates-Albers LM, Vu NT, Hanas RJ, Kupiec TC, Brackett DJ, and Hanas JS. (2011) Serum discrimination of early-stage lung cancer patients using electrospray-ionization mass spectrometry. Lung Cancer 74, 206– 211.
- Hocker, J.R., Lerner, M.R., Mitchell, S.L., Lightfoot, S.A., Lander, T.J., Quillet, A., Hanas R.J., Peyton, M.D., Postier, R.G., Brackett, D.J, and Hanas, J.S. (2011) Distinguishing early clinical stages of pancreatic cancer using Serum profiling. Cancer Investigation 29, 173-179.
- Hanas, J.S., Briggs, G.B., Learner, M.R., Lightfoot, S.A., Larabee, J.L.,Epstein, R.H., Karsies, T., Hanas, R.J., Brackett, D.J., and Hocker, J.R. (2010). Systemic Molecular and Cellular Changes induced in Rats upon Inhalation of JP-8 Petroleum Fuel Vapor. Toxicology Mechanisms and Methods, 20, 204-212.
- Larabee, J.L., Hocker, J.R., and Hanas, J.S. (2009). Mechanisms of inhibition of zinc- finger transcription factors by selenium compounds ebselen and selenite. J. Inorg. Biochem. 103, 419-426.
- Smith BJ, Lightfoot SA, Lerner MR, Denson KD, Morgan DL, Hanas JS, Bronze MS, Postier RG, Brackett DJ. (2009) Induction of cardiovascular pathology in a novel model of low-grade chronic inflammation. J. Cardiovascular Pathology, 18, 1-10.
- Larabee, J.L., Hocker, J.R., Cheung, J.Y., Gallucci, R.M., and Hanas, J.S. (2008) Serum Profiling of Rat Dermal Exposure to JP-8 Fuel Reveals an Acute-Phase Response. Toxicology Mechanisms and Methods, 18, 41-51.
- Hanas, J.S., Hocker, J.R., Cheung, J.Y., Larabee, J.L., Lerner, M.R., Lightfoot, S.A., Morgan, D.L., Denson, K.D. , Prejeant, K.C., Gusev, Y., Smith, B.J., Hanas, R.J., Postier, R.G. , and Brackett, D.J. (2008) Biomarker Identification in Human Pancreatic Cancer Sera. Pancreas 36, 61-69.
- Hanas, J.S., Hazuda, D.R., Bogenhagen, D.F., Wu, F.H.-C. and Wu, C.-W. (1983) Xenopus transcription factor A requires zinc for binding to the 5S RNA gene. J. Biological Chemistry 258, 14120-14125.
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