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Faculty & Research

Michael A. Collins, Ph.D.
Professor                                                 collins mi.TIF (1624152 bytes)

A.B., University of Vermont (1962)
Ph.D., Purdue University (1968)
Postdoctoral Fellow, Columbia University College of Physicians and Surgeons

Research in the Collins' laboratory, done in collaboration with Dr. E.J. Neafsey, neuroanatomy professor, focuses on brain neurodegeneration and/or neuroprotection mechanisms during (a) alcohol intake and (b) parkinsonism.  (a) Daily "binge" exposure to high alcohol levels causes cortical and hippocampal degeneration in vivo (adult rats) and in organotypic rat brain slices in long-term culture.  The binge alcohol-induced neurodamage appears to involve brain hydration rather than synaptic excitotoxicity, since diuretic agents that prevent brain edema are neuroprotective whereas antagonists to glutamate receptors, calcium channels, and nitric oxide are not.  Initial findings indicate that alcohol bingeing promotes a glial-dependent, neuroinflammatory-like process involving TNF alpha, arachidonic acid, and oxidative stress.  In contrast, pre-conditioning brain cultures with moderate (non-toxic) levels of alcohol inhibits several potent neurotoxins such as HIV-1 proteins gp120, Tat or gp41, or Alzheimer's disease protein, beta-amyloid.   This novel alcohol pre-conditioning neuroprotection may result in part from suppression of glial mechanisms initiated by these neurotoxins, as well as from elevations in neuroprotective heat shock proteins.  (b) Since Parkinson's disease has an environmental component, we have studied with rodents and brain cultures whether relatively common heterocyclics found in foods and smoke (beta-carbolines, e.g. norharman) are pro-neurotoxins that may act like MPTP which is a synthetic N-methylated pyridine used to cause parkinsonism in animal models.  We and others have shown that brain enzymes can N-methylate carbolines, that the N-methylated products are neurotoxic in vivo and in vitro in rats, and that methylated carbolines appear elevated along with N-methylase activity in parkinsonian brain.

View list of Dr. Collins' publications through the National Library of Medicine's PubMed online database.

Allen Frankfater, Ph.D.
          Professor                                  Frankfater_a.jpg (126915 bytes)

B.S., Brooklyn College-City University of New York (1963)
Ph.D., Duke University (1968)
Postdoctoral Fellow, University of Chicago

Dr. Frankfater's research interests concern the regulation of lysosomal proteinase synthesis and trafficking
in tumor cells and how they might facilitate tumor cell metastasis. These secreted proteinases can promote tumor cell invasion by degrading extracellular barriers to migration. His laboratory has focused on the proteinase enzyme cathepsin B, which is seen to be elevated in a number of highly metastatic tumors of humans and mice. Utilizing techniques of biochemistry, cell biology and molecular biology, his laboratory is seeking to elucidate the reasons for the increased expression of cathepsin B in metastatic tumors, and to identify defects in the intracellular transport of cathepsin B which leads to its aberrant secretion. Recent studies have focused on the identification of the cathepsin B gene promoter and promoter-specific binding proteins responsible for the regulation of cathepsin B expression in tumors. Also ongoing is research into the role of the mannose-6-phosphate/insulin-like growth factor II receptor in cancer. This receptor has the dual function of correctly targeting lysosomal proteinases to the lysosome and of controlling circulating levels of the potent growth factor, IGF-II. The frequent finding that this receptor is mutated in tumors can explain their increased secretion of lysosomal proteinases. His laboratory is now also investigating the role of the IGF-II receptor in regulating tumor growth.

View a list of Dr. Frankfater's publications through the National Library of Medicine's PubMed online database.

Mary Druse-Manteuffel, Ph.D. 
         Professor       Manteuffel_Mary 1.tif (1967444 bytes)

A.B., Duke University (1968)
Ph.D., University of North Carolina (1972)
Postdoctoral Fellow, National Institutes of Health

Dr. Druse-Manteuffel's laboratory has been interested in understanding the causes of the CNS damage that accompanies maternal alcohol consumption and exploring the possibility that some of the damage might be prevented by a therapeutic treatment. The major research emphasis of this laboratory has been the elucidation of the mechanism(s) by which ethanol impairs the development of the serotonin (5-HT) system and causes apoptosis to 5-HT neurons. Recent research focuses on the deleterious effects of ethanol on pro-survival and anti-apoptotic pathways. Additional studies examine cellular signaling pathways that mediate the neuroprotective effects of a 5-HT-1A agonist and of specific antioxidants. These in vivo and in vitro investigations use a combination of techniques, including cell culture, immunohistochemistry, western blots and real-time RT-PCR .

View list of Dr. Druse-Manteuffel's recent publications through the National Library of Medicine's PubMed online database.

Richard M. Schultz, Ph.D.
         Professor                           Schultz_R.JPG (84787 bytes)

B.A., State University of New York at Binghamton (1964)
Ph.D., Brandeis University (1969)
Postdoctoral Fellow, Harvard University Medical School

Dr. Schultz is interested in how activated oncogenes control the expression of genes required for the malignant properties of the tumor cell. For example, protease genes are highly expressed and are essential for the invasion and metastasis of tumor cells. We have shown the biochemical pathways required for the expression of different protease-invasive tumor cell phenotypes. Our characterization of different protease-invasive phenotypes in ras-transformed fibroblasts showed how alternative phenotypes can be generated by changes in the activities of ras-oncogene activated downstream biochemical pathways, resulting in different sets of expressed genes. These phenotypes can switch between each other on stimulation by exogenous signals or through additional mutations. Furthermore, the different malignant phenotypes regulate programmed cell death (apoptosis) by different biochemical mechanisms. My laboratory is investigating the properties of these ras oncogene pathways and how they can be manipulated to selectively regulate the properties of the malignant cell.

View list of Dr. Schultz's publications through the National Library of Medicine's PubMed online database.

William H. Simmons, Ph.D.
         Professor                 Simmons_Williams Ph.D.tif (2436699 bytes)

B.A., Wittenberg University (1969)
Ph.D., University of Illinois Medical Center (1979)
Postdoctoral Fellow, University of Illinois Medical Center

Dr. Simmons' research program centers on the study of enzymes called proteases which split proteins and peptides into smaller units. His laboratory is determining which proteases in lung and heart are responsible for degrading the strong hypotensive hormone, bradykinin, thus destroying the ability of this hormone to lower blood pressure and protect the heart from damage during a heart attack. The major focus of the lab is on an enzyme called aminopeptidase P which inactivates bradykinin by cleaving off its first amino acid.  This enzyme has been purified and studied in detail, and a specific inhibitor called apstatin has been synthesized.  Apstatin can increase the effects of bradykinin by preventing its degradation.  Apstatin has been shown to greatly reduce the damage that occurs in an experimentally-induced heart attack in the rat.  Studies are underway to determine if aminopeptidase P is also an important bradykinin-degrading enzyme in humans.  New inhibitors of this enzyme are being designed that bind more tightly to the enzyme and that also can be administered as a drug by mouth.  The goal is to invent a drug that is useful in treating cardiovascular diseases which remain the most common causes of death in this country.  Two U.S. patents have been granted on this work.

View list of Dr. Simmons' publications through the National Library of Medicine's PubMed online database.

Maurizio Bocchetta, Ph.D.   
         Assistant Professor
         Thoracic Oncology Research Program
         Cardinal Bernardin Cancer Center         

B.S., University of Rome (1991)
Ph.D., University of Rome (1996)
Postdoctoral Fellow, University of Illinois (1996-98)

In the last eight years I have worked on the hypothesis that Simian Vacuolating virus 40 (SV40) participates to the pathogenesis of a very aggressive Thoracic malignancy (human malignant mesothelioma). I have discovered that primary human mesothelial cells are uniquely susceptible to SV40-mediated malignant transformation and that SV40-mediated transformation of these cells can lead to tumor formation in immunocompromized mice (data to be published). Through studying the molecular mechanisms leading to SV40-mediated malignant transformation of human mesothelial cells, I found that the evolutionarily conserved Notch signaling pathway plays a major role in SV40 malignant transformation and in the pathogenesis of malignant mesothelioma. Currently, my research interests include: the study of Notch signaling in mesothelioma, in other thoracic malignancies (e.g., non-small cell lung cancer), the mechanisms of interactions between the SV40 major oncogene (the Large T antigen) and key cell cycle regulators of human cells.

Selected Publications:
Chen, Y, DeMarco, M.A., Graziani, I., Gazdar, A.F., Strack, P.R., Liele, L., Bocchetta, M. "Oxygen concentration determines the biological effects of Notch-1 signaling in adenocarcinoma of the lung.  Cancer Res. 2007, in press.
    Bocchetta M., Miele L., Pass H.I. and Carbone M. “Notch-1 induction, a novel activity of SV40 required for growth of SV40-transformed human mesothelial cells”.  Oncogene.  2003;22:81-89.
     Carbone M., Burck C., Rdzanek M., Rudzinski J., Cutrone R. and Bocchetta M. "Different susceptibility of human mesothelial cells to polyomavirus infection and malignant transformation". Cancer Res.   2003;63: 6125-6129.

View list of Dr. Bocchetta's publications through the National Library of Medicine's PubMed online database.

Mitchell F. Denning, Ph.D.   
        denning.gif (23097 bytes)  Professor

B.S., University of Arizona (1986)
Ph.D., University of Wisconsin-Madison (1991)

The research in Dr. Denning's laboratory is focused on
skin carcinogenesis. Non-melanoma skin cancers (basal and squamous cell carcinoma) are the most common human malignancy. We are dissecting the signal transduction pathways which regulate normal skin homeostatsis to better understand how alterations in these signaling pathways contribute to malignancy.  In particular, we are focusing on the protein kinase C (PKC) family of serine/threonine kinases. PKC is a central regulator of the normal keratinocyte differentiation program, and alterations in epidermal differentiation and PKC signaling are evident in malignant keratinocytes. PKC is also activated by phorbol ester tumor promoters commonly used in mouse skin chemical carcinogenesis studies. Recently, we demonstrated that PKC is also activated by ultraviolet radiation, the main environmental carcinogen for human skin cancer formation. A variety of cell biological, biochemical, pharmacological, and molecular genetic approaches are being used to characterize the functional significance of PKC activation/inactivation in normal and neoplastic keratinocytes.

View list of Dr. Denning's publications through the National Library of Medicine's PubMed online database.

Manuel O. Diaz, M.D.  
         Professor                                               Diaz1.gif (100014 bytes)

B.A., Preparatory Institute Eduardo Acevedo, Uruguay (1957)
I.icenciado en Biologia, University of the Republic of Uruguay (1972)
M.D., University of the Republic of Uruguay (1976)

Dr. Diaz's laboratory is trying to answer several questions about the process of replicative senescence. What is the role of p16, a cell cycle inhibitor, in this process? How is p16 expression regulated during senescence? In order to answer these questions, we are studying the p16 gene promoter and associated transcription factors. The system studied is an in vitro culture of activated human peripheral blood T cells that senesce after about 20 population doublings. In a related project, the role of telomerase and telomeric proteins in the regulation of telomere length is being studied. Telomere shortening is believed to be one of the triggers of replicative senescence. We are also interested in the role of telomerase and telomere shortening in genomic instability during oncogenesis. A separate project is the role of the MLL gene in the regulation of gene expression during commitment and differentiation of hematopoietic cell lineages. The MLL gene is involved in chromosomal translocations in human leukemia that convert it into a dominant oncogene. MLL is a vertebrate homolog of the Drosophila trithorax (trx) gene. Trx mutants have a homeotic phenotype, due to misregulation of HOX gene expression. MLL mutation in mouse also produces a homeotic phenotype with segmental transformations of the axial skeleton. We are studying proteins that associate with different domains of MLL and apparently modulate its transactivating activity.

View list of Dr. Diaz's publications through the National Library of Medicine's PubMed online database.

Andrew K. Dingwall, Ph.D.
         Associate Professor

B.S., University of Wyoming, Laramie (1982)
M.S., Microbiology and Biochemistry, University of Wyoming, Laramie (1984)
Ph.D., Molecular Genetics, Albert Einstein College of Medicine, Bronx, NY (1989)

Postdoctoral Fellow, Stanford University School of Medicine, Stanford, CA., Departments of Developmental Biology, Genetics and HHMI (1989-91, 1991-1996)

We study a highly conserved group of proteins that form a complex whose main function is to regulate gene expression through direct effects on chromatin structure. When components of this complex are missing or mutated, cells lose the ability to properly control their fates and growth, leading to a variety of diseases including aggressive cancers. The best studied of these complexes is the highly conserved SWI/SNF complex, found in yeast, flies and mammals, that is required for the activation of many, but not all genes. Our projects utilize molecular, genetic and biochemical analysis of the Drosophila SWI/SNF complex, known as the Brahma (BRM) complex. The efforts are focused on one of the most highly conserved and critically important components, known as SNR1. This subunit is crucial in both flies and humans for coordinating or targeting specific protein interactions between the complex and a variety of transcription factors and cell cycle regulatory proteins. We isolated a temperature sensitive snr1 mutant that allows for conditional removal of snr1 function, allowing us to fully characterize the biological requirements for SNR1 during development. This is especially important as the snr1 gene is essential in flies and loss of its human counterpart INI1 has been directly linked with aggressive childhood cancers and T-cell lymphomas. Thus, SNR1/INI1defines a new class of extremely potent tumor suppressors that function to regulate chromatin accessibility.

Representative publications by Dr. Dingwall   View a list of Dr. Dingwall's publications through the National Library of Medicine's PubMed online database.

Lydia L. DonCarlos, Ph.D.Doncarlos_Lydia.jpg (134820 bytes)

B.A., Summa Cum Laude, Anthropology, 1977. University of Oklahoma.
M.A., Anthropology, 1979. University of Oklahoma.
Ph.D., Neurobiology, 1985. Kent State University.
Postdoctoral Fellow, University of Rochester, 1986-1987. National Institute on Aging fellowship
Postdoctoral Fellow, Institute of Animal Behavior, Rutgers University, 1987-1990 National Research Service Award From NIMH.

The main focus of our laboratory is to understand sexual differentiation of the brain as a model for how the external environment influences development of the nervous system. In mammals, induction of the masculine neuronal phenotype depends on the presence of androgens, derived from the testes; in the absence of androgens, the phenotype of the brain is essentially feminine. Androgens, estrogens, and other steroid hormones exert effects through steroid-specific receptors; the expression of these receptors, which are ligand-dependent transcription factions, is highly regulated. Many behaviors and physiological functions such as reproduction, language, spatial learning and stress responses, are sexually differentiated. Moreover, many mental and neurological disorders are more prevalent in one gender than the other.
Histochemical, molecular, and behavioral experiments in our laboratory are aimed at understanding the role of steroid receptors in modulating specific developmental processes such as neurogenesis, neurite outgrowth, selection of neurotransmitter phenotype, and cell death and the impact of these alterations on functional sexual differentiation. In addition, we are exploring the role of gonadal hormones in neuronal survival following injury, and are investigating the impact of estrogen on mood disorders.
An understanding of the specific mechanisms through which gonadal steroids impact on functional differentiation of the central nervous system may elucidate the etiology of sexually differentiated psychological and neurological disturbances. Further, this research may offer clues as to the relative contributions of environmental and biological factors in the onset of gender-based differences in mental health and disease.

View list of Dr. DonCarlos' publications through the National Library of Medicine's PubMed online database.

Mary Ann Emanuele, M.D.
Emmanuel.jpg (4808 bytes)

B.S., Marquette University of Milwaukee (1972)
M.D., Loyola University Stritch School of Medicine (1975)

Our laboratory has been investigating the impact of acute and chronic ethanol exposure on the hypothalamic pituitary testicular axis in male rodents as they progress through puberty into adulthood.  These studies include assessment of basal and stimulated luteinizing hormone releasing hormone (LHRH), pituitary Luteinizing Hormore (LH) and Follicle Stimulating Hormone (FSH), and testosterone.  The mechanism(s) for the suppression of the reproductive unit are being pursued, including the role of nitric oxide, beta-endorphin, and oxidative injury in addition to preventive modes of therapy such as naltrexone and antioxidants.  Also being explored are the effects of ethanol on the growth hormone-IGF-1 axis.  A second area of investigative research is the effect of insulin on thermal injury in the murine model after ethanol exposure.  In these studies, hypothalamic, pituitary, adrenal, and hepatic cytokines are assessed in addition to wound healing.  Mechanisms for the beneficial effects of insulin are being pursued, including effects on NfKB, STAR and FAS/FAS ligand.

View list of Dr. Emanuele's publications through the National Library of Medicine's PubMed online database.

Kimberly O. Foreman, Ph.D.
Associate Professor

B.A., Miami University (1987)
Ph.D., University of Cincinnati (1993)
Postdoctoral Fellow, University of Michigan (1993-95)

 Dr. Foreman's research focuses on Notch signaling in human malignancies, particularly breast cancer.  Activated Notch is found in breast cancer tissue samples, and overexpression of Notch receptors and ligands is associated with a poor prognosis.  These findings suggest Notch plays an important role in breast cancer tumorigenesis, and Dr. Foreman's laboratory is working from the hypothesis that Notch signaling is a potential therapeutic target for cancer treatment.  Currently, her laboratory is focussed on two areas of investigation:  Notch signaling and angiogenesis; Notch signaling in breast tumor initiating cells (also referred to as cancer stem cells).

Dr. Foreman has authored over 37 publications in peer-reviewed journals.  In addition to her research efforts, she is actively involved in medical student, graduate student, and resident education at Loyola.

View list of Dr. Foreman's publications through the National Library of Medicine's PubMed online database.

Charles Hemenway, MD

B.A., Middlebury College (1981)
M.D., University of Massachusetts (1987)
Ph.D., Duke University (1996)

Dr. Hemenway received his medical degree from the University of Massachusetts Medical School.  He completed a combined residency in Internal Medicine and Pediatrics at the University of Florida in Gainesville after which he began fellowship training in Pediatric Hematology/Oncology at Duke University.  During the course of fellowship training, he developed an active interest in basic research and remained at Duke for five years where he received a PhD in Genetics.

In 1996, he joined the Department of Pediatrics at Tulane University in New Orleans.  There he established a research laboratory while participating actively in clinical care and medical education.  He focused his research on acute leukemias characterized by rearrangements of the MLL gene with a specific interest in developing small molecular inhibitors of abnormal MLL gene products.

In 2007, he moved to Loyola University Chicago where he was named the Ronald McDonald House Charities Endowed Professor in Pediatric Hematology/Oncology.  His work in the Oncology Institute of the Cardinal Bernardin Cancer Center continues to center on the rational design of inhibitors of MLL leukemias.

View list of Dr. Hemenway's publications through the National Library of Medicine's PubMed online database.

Jeffrey R. Kanofsky, M.D., Ph.D.
         Professor    Kanofsky_Jeffrey M.D.Ph.D.tif (6577830 bytes)

B.S., Illinois Institute of Technology (1968)
Ph.D., Illinois Institute of Technology (1972)
M.D., Rush Medical College (1975)

Dr. Kanofsky studies the role of singlet oxygen in biological systems. Singlet oxygen is an electronically excited oxygen molecule that reacts rapidly with a wide variety of biological molecules and consequently is highly toxic. Specialized instrumentation is available in this laboratory for measuring singlet oxygen in complex biological systems using the characteristic singlet-oxygen phosphorescence at 1270 nm. Recent work has focused on applications of singlet-oxygen biochemistry of relevance to medicine.   Several cationic carotenoid derivatives have been sythesized.  In cultured cells, these synthetic carotenoid derivatives have been found to be more effective in preventing photosensitizer-induced cell damage than natural carotenoids.  It is hypothesized that the synthetic carotenoid derivatives are more effective because they concentrate in certain critical areas of the cell.  The synthetic carotenoid derivatives are felt to be models for drugs that might prevent certain photosensitivity disorders, such as the porphyrias, certain phototoxic drug reactions and macular degeneration.

View list of Dr. Kanofsky's publications through the National Library of Medicine's PubMed online database.

    Elizabeth J. Kovacs, Ph.D.

B.A., Reed College (1978)
Ph.D., University of Vermont (1984)
Postdoctoral Fellow, National Cancer Institute

Overall focus:  The effects of gender, aging, and alcohol exposure on inflammation and cell mediated immunity.

  1. Immunosenescence:  Age-dependent defects in Toll-like receptor (TLR) mediated signal transduction pathways, including mitogen activated protein (MAP) kinases in macrophages.  Pulmonary inflammatory responses after injury in young vs. aged subjects.  Sex differences and hormone replacement alter inflammatory and immunity after burn injury in the aged.
  1. Sex differences in cell mediated immune responses after injury:  Mechanism(s) by which estrogen, testosterone, and glucocorticoids modulate neutrophil, macrophage and T lymphocyte function after burn injury and/or infection.   
  1. Alcohol and immune responses after injury and/or infection:  Systemic and organ-specific inflammatory response after burn injury with or without infection.  Effects of combined insult of ethanol and burn injury on cell-mediated immune function.  Ethanol and TLR-mediated signal transduction leading to the production of pro-inflammatory and immunoregulatory cytokines by macrophages. 
  1. Pulmonary response to smoke inhalation and infection after burn injury.  Effect of inhalation injury on acute lung injury and acute respiratory distress syndrome and the local and systemic production of inflammatory and fibrogenic cytokines.
  1. Effects of combined radiation and burn injury on pulmonary and intestinal inflammation and barrier function.

View list of Dr. Kovacs' publications through the National Library of Medicine's PubMed online database.

Caroline LePoole, Ph.D.
         Research Assistant Professor

M.S., Utrecht University (1987)
Ph.D. Amsterdam University (1993)
Postdoctoral Fellow, Amsterdam University (1993-1995)

Autoimmune recognition of melanocytes in vitiligo is a primary research interest of Dr. Le Poole, as well as dendritic cell effector functions and immune recognition of tumor cells.  The progressive loss of skin color as observed in vitiligo is considered a positive prognostic factor in patients with malignant melanoma, where the immune response all to often fails to clear patient of their tumor.  By studying effective recognition of melanocytic cells in vitiligo, Dr. Le Poole aims to contribute to the development of new anti-melanoma vaccines. 
Dr. Le Poole has authored 50 book chapters and publications in peer reviewed scientific journals.  She was elected secretary of the Chicago Association of Immunologists (2000-2002), and her current activities include the Directorship of the Immune Monitoring Core in the Cardinal Bernardin Cancer Center where patient immune responses to experimental vaccines are characterized and quantified.

View list of Dr. Le Poole's publications through the National Library of Medicine's PubMed online database.

   Ruben Mestril, Ph.D.
  mestril.gif (83994 bytes)Associate Professor

B.A., St. Thomas University (1981)
Ph.D., University of Miami (1986)
Postdoctoral Fellow, German Cancer Research Center

Research interests of this laboratory concentrate on the function of the heat shock proteins (HSP) in mammalian cells and more specifically their protective role in cardiac and myogenic cells during ischemic stress. We have constructed a transgenic mouse line that contains a novel rat inducible HSP70 gene that we previously cloned and characterized. This transgenic mouse line expresses high levels of the exogenous rat HSP70 in heart, skeletal muscle and brain tissue as assessed by Western blot analysis. We have tested if the increased presence of HSP70 in the hearts of these transgenic mice confers tolerance to ischemic/reperfusion injury and found this to be the case. Furthermore, we have generated adenovirus vectors that contain the rat HSP70 gene under the control of the human CMV enhancer which we have now shown confer tolerance to simulated ischemia to myogenic cells and cardiomyocytes infected with this construct. We are presently infusing this adenoviral construct into the hearts of experimental animals to confirm the results obtained in the mouse heart. The possibility that an increase in expression of an endogenous heat shock protein within the cardiac cell is able to confer resistance against ischemia is exciting and warrants the pursuit of means of inducing the expression of these proteins by using non-noxious drugs and gene therapy approaches.

View list of Dr. Mestril's publications through the National Library of Medicine's PubMed online database.

Gregory A. Mignery, Ph.D.  
Associate Professor

B.S., Purdue University (1981)
Ph.D., Texas A&M University (1987)
Postdoctoral Fellow, University of Texas Southwestern Medical Center at Dallas

This lab's research aims have focused on the structure/functional characterization of the inositol 1,4,5-trisphosphate receptor (InsP3R) protein family.   My laboratory has recently completed initial comparisons of native type-1 and type-2 channels from cerebellar and cardiac tissues as well as two splice variants of the recombinant type-1 receptor. We are currently constructing and characterizing a collection of InsP3R sub-type chimeras designed to investigate which sequence domains confer functional heterogeneity between receptor isoforms. In addition, my laboratory is investigating several interesting facets of the receptor, which include: the role of the multiple determinants involved in receptor subunit oligomerization and channel formation, the characterization of a novel InsP3 indicator, and yeast two-hybrid screening for protein-protein interactions. The long-term goal of my laboratory is to integrate cell/molecular biological and biophysical methodologies as tools to decipher the regulation and role of proteins that govern intracellular calcium signaling dynamics.

View list of Dr. Mignery's publications through the National Library of Medicine's PubMed online database.

  Clodia Osipo, Ph.D.   
           Assistant Professor           

 B.S., Mundelein College (1988)
 B.A., Mundelein College (1988)
 Ph.D., Loyola University Chicago (2002)
 Postdoctoral Fellow, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Feinberg School of Medicine

 My lab is focused on elucidating crosstalk between ERBB2 and Notch 1 in Breast Cancer and the significance on current and future drug therapies.

View a list of Dr. Osipo's publications through the National Library of Medicine's PubMed online database.

     Toni Pak, Ph.D.
            Assistant Professor

B.A., University of Colorado at Boulder (1995)
M.A., University of Colorado at Boulder (1997)
Ph.D., University of Colorado at Boulder (2002)

The central theme of my research falls under the broad category of neuroendocrinology with a specific focus on the molecular signaling properties of nuclear steroid receptors and the process of sexual maturation.  Elucidating the molecular basis of nuclear steroid receptor-mediated gene expression is central to understanding how steroid hormones modulate a variety of physiological processes including social behaviors, sexual maturation, and reproductive function.  Research in my lab integrates molecular techniques with whole animal physiology in order to determine how gene expression and hormones interact to regulate the process of puberty.

There are currently three main projects in the lab.  The first one involves elucidating the molecular signaling pathway for estrogen receptor-beta (ERβ) by addressing the following questions: 1) how do the ERb splice variants interact with each other to modulate estrogen signaling and 2) what are the molecular mechanisms governing ERb splice variant-induced gene transcription.  Recent work has shown that ERβ has strong ligand-independent activity.  Insight into the cellular and molecular consequences of these ligand-independent effects will provide another dimension to our general knowledge of steroid hormone action. 

Second, a dramatic increase in gonadotropin-releasing hormone (GnRH) is one of the hallmarks of pubertal onset.  Research in this laboratory uses a transgenic rat model that expresses green fluorescent protein under the control of the GnRH promoter in order to identify candidate genes in GnRH neurons that are differentially regulated during the process of sexual maturation. 

Finally, centrally expressed nuclear steroid hormone receptors are important integrators of the internal and external factors that potentiate downstream centrally mediated behaviors.  Previous work demonstrated that ERβ and its splice variants modulate arginine vasopressin (AVP) promoter activity in neuronal cells; an important central mediator for social, aggressive and affiliative behaviors. Recent work has focused on determining 1) how hormones affect AVP expression during pubertal development and 2) how does “binge drinking” during puberty affect AVP expression in the brain.  In addition, recent work has begun to investigate how changes in gonadal steroid hormones at the time of puberty contribute to the sexually dimorphic patterns of alcohol consumption.

To visit Dr. Pak's web site, please go to the following:  www.tonipak.com

 View a list of Dr. Pak's publications throug the National Library of Medicine's PubMed online database.

  Erika S. Piedras-Rentería, Ph.D.  Erika_Piedras-Renteria.jpg (8573 bytes)
         Assistant Professor

B.S.,Universidad Autónoma, Metropolitana, México (1986)
M.S., Universidad Autónoma, Metropolitana, México (1989)
Ph.D., University of Illinois (1996)
Postdoctoral Fellow, Stanford University

Molecular mechanisms of neuronal calcium channel function in normal and pathological conditions.  Neuronal calcium entry starts and regulates critical cellular events such as neuronal excitability, neurotransmitter release, and/or neuronal gene expression.  The P/Q-type calcium channel (CaV2.1 or alpha1A) is an essential presynaptic molecule; it mediates voltage-dependent calcium influx thereby coordinating neuronal excitation and neurotransmitter release in neurons. The importance of the P/Q type channel role in synaptic transmission and calcium homeostasis is evidenced by the fact that mutations in this channel protein often lead to pathological conditions such as familial migraine, seizures, epilepsy and ataxia.

My lab is interested in understanding calcium channel function in normal and in pathophysiological conditions.  In one of our projects, we study the role of the P/Q-type channel in synaptic transmission and the mechanisms of channel malfunction when mutations leading to Spinocerebellar Ataxia Type 6 are present.  Spinocerebellar ataxia type 6 is a neurodegenerative disease caused by the presence of longer than normal polyglutamine expansions (trinucleotide repeat disease) in the carboxyl terminus of the P/Q channel.  The methods we use combine biology, biochemical and cell biology assays to design probes, measure protein levels and assay calcium cytoxicity in the presence of mutated channels.  We use fluorescence measurements and electrophysiological recordings (whole-cell patch clamp experiments) to assay channel activity, localization, biophysical properties and physiological function during synaptic vesicle release.

Representative publications by Dr. Piedras-Rentería 

View list of Dr. Piedras-Renteria's publications through the National Library of Medicine's PubMed online database.

George J. Siegel, M.D.
Siegel_GeorgeM.D.tif (11341938 bytes)               

B.A., Yeshiva College (1957)
M.D., University of Miami School of Medicine (1961)
Research Associate, NINDS

Current research activities of Dr. Siegel and associates
1) Immunoneutralization of amyloid peptide neurotoxicity in rodent models of Alzheimer's disease.
2) Neurotrophic factors in the aging nervous system and in Alzheimer's, Parkinson's and other neurodegenerative diseases.

View list of Dr. Siegel's publications through the National Library of Medicine's PubMed online database.

Evan B. Stubbs, Jr., Ph.D.
         Associate Professor                           
stubbs.jpg (36324 bytes)

B.S., University of Illinois (1981)
Ph.D., University of Missouri (1987)
Postdoctoral Scholar, University of Michigan

Studies performed in Dr. Stubbs’ laboratory examine immune-mediated mechanisms of peripheral nerve disease associated with monoclonal gammopathy of undetermined significance (MGUS), a non-cancerous B cell proliferative disorder that is strikingly prevalent among the aging population. Debilitating complications of peripheral neuropathy with resultant decreased quality of life have been reported in up to 50% of MGUS patients. Despite the frequency and clinical significance of MGUS neuropathy, a cause for the peripheral nerve dysfunction observed in a majority of these patients has not been determined. 

Dr. Stubbs and colleagues are c
urrently funded to determine the significance of anti-neural antibody isotypes in sera of MGUS patients with peripheral neuropathy. Their studies have identified novel pathogenic anti-neural polyclonal antibodies in sera from patients with IgG MGUS neuropathy. These antibodies were found to be distinct from the patients’ monoclonal IgG paraprotein, a novel finding that uniquely distinguishes IgG MGUS neuropathy from IgM MGUS neuropathy.  

The clinical importance of these studies is that it may be possible to develop therapeutic strategies to detect and specifically remove pathogenic anti-neural antibodies from sera of MGUS patients at risk for antibody-mediated nerve injury.

View list of Dr. Stubbs' publications through the National Library of Medicine's PubMed online database.

WitteP.jpg (145894 bytes)

  Pamela Witte, Ph.D.

B.S., Stephen F. Austin State University, Texas (1973)
Ph.D., Southwestern Graduate School of Biomedical Science, University of Texas (1984)
Postdoctoral Fellow, Oklahoma Medical Research Foundation
Postdoctoral Fellow, University of Texas Southwestern Medical Center
Fellow, Leukemia Society of America


Our lab is interested in the impact of aging on the cellular and molecular regulation of B-lymphocyte development and B-cell homeostasis.  B-cells form and reach an immature, but responsive stage, in the hemopoietic tisssues of fetal liver and postnatal bone marrow.  Soluble factors (cytokines, growth factors and chemokines) involved in the differentiation and expansion of early B-cells are produced by hemopoietic microenvironmental cells.  Through work done in this laboratory, we have identified, isolated and studied bone marrow microenvironmental cells (called stromal cells) that support B-cell development.  We have established the kinetics of B-cell production as the cells transition and mature from bone marrow to the spleen in aged mice.  We are currently pursuing issues involving changes in the aged tissue that affect the migration and function of different stages of B-cells.  Additionally, we have found that bone marrow stromal cells augment the survival of long-lived plasma cells, which provide a foundational source of antibodies for immune protection.  Our major research goals are: (1) to determine how the production and maintenance of B-cells is altered by normal physiologic events, such as aging, and (2) to examine the hypothesis that stromal cells are a key regulator of lymphopoiesis in the marrow, (3) to identify the mechanisms that allow stromal cells to support the longevity of plasma cells in the bone marrow, and (4) to explore the mechanisms whereby such highly metabolic cells such as plasma cells can survive for many years. 

View list of Dr. Witte's publications through the National Library of Medicine's PubMed online database.

Nancy J. Zeleznik-Le, Ph.D.   


         B.S., Ohio State University (1982)
         Ph.D., Duke University (1988)
         Postdoctoral Fellow, University of North Carolina,
           Chapel Hill

Dr. Zeleznik-Le received her Ph.D. (Cellular and Molecular Biology/Immunology) from Duke University in 1988.  She continued her training as a postdoctoral fellow at the Lineberger Cancer Center, University of North Carolina-Chapel Hill in the laboratory of Dr. Jenny Ting, working on MHC Class II gene regulation.  In 1991, Dr. Zeleznik-Le became a Research Associate (Instructor) and then in 1993, a Research Associate (Assistant Professor) at the University of Chicago, working with Dr. Janet Rowley.  She started her work on the Mixed Lineage Leukemia (MLL) gene and protein while at the University of Chicago.  In 1999, she joined the faculty at Loyola University Medical Center as an Assistant Professor in the Hematological Malignancies Program.  In 2003, Dr. Zeleznik-Le was promoted to Associate Professor, and then in 2009 to Professor.  Dr. Zeleznik-Le holds a primary appointment in the Department of Medicine, and has adjunct appointments in two graduate programs, Molecular Biology and Molecular and Cellular Biochemistry.

Dr. Zeleznik-Les research interest is focused on the MLL protein, and on MLL fusion proteins that cause leukemia.  MLL is involved in the proper maintenance of expression of many downstream target genes, including genes of the HOX cluster.  How MLL functions to help maintain proper expression of target genes is thought to involve epigenetic mechanisms acting at the level of chromatin.  One focus of her work is to identify epigenetic changes (DNA methylation and histone protein modifications) that are mediated by MLL and MLL fusion proteins.  This also includes studies to understand how proteins that interact with MLL compete and /or synergize to mediate these effects, and the role of post-translational modifications of MLL on its function.  Her lab utilizes molecular biological and biochemical approaches as well as in vitro and in vivo murine models of MLL leukemia to dissect critical functions required for immortalization and leukemogenesis.  Questions addressed concern hematopoietic cell lineage commitment, specificity of MLL and partner gene functional domains, and transcriptional elongation pathways contributing to immortalization capability.  One goal of this work is development of novel therapeutic approaches for these aggressive leukemias.

Dr. Zeleznik-Le has been involved in the cloning of several MLL fusion genes from patient leukemia samples.  She has developed murine models of MLL leukemia that recapitulate the human disease.  Her laboratory has identified proteins that interact with MLL, including those with chromatin modifying capability, and they are involved in collaborative studies to identify small molecules that might function therapeutically. 

Dr. Zeleznik-Le is the author of over 50 publications. She is active in training graduate students, both as a teacher and as a research mentor.  Her research is supported by grants from NCI and NHLBI of the National Institutes of Health.  She is also involved in laboratory correlates for some early stage clinical trials of epigenetic modifiers.

              View list of Dr. Zeleznik-Le's publications through the National Library of
              Medicine's PubMed online database.

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