Samar Basu, Ph.D.

"Eicosanoids- An evidenced link to oxidative stress and inflammation"

Samar Basu, Ph.D.
Oxidative Stress & Inflammation
Department of Public Health and Caring Sciences
Uppsala University
Daghammarskjöldsväg 14B
Uppsala Science Park
SE-751 85 Uppsala
Sweden
Tele: + 46 18 6117958
Email: samar.basu@pubcare.uu.se

Professional Summary: 

Samar Basu is an Associate Professor and Head of the Research Group, Oxidative Stress and Inflammation at the Medical Faculty, Uppsala University, Sweden, and also a Visiting Scientist at the Harvard Medical School, Boston. He obtained his M.Sc. (Reproductive Endocrinilogy, 1984) and Ph.D. (Reproductive Endocrinology/Obstetric and Gynaecology, 1988) from the Veterinary Medical Faculty in Uppsala under supervision of Prof. Hans Kindahl who is a decendent from Prof. Bengt Samuelsson’s prostaglandin laboratory at the Karolinska Institute, Stockholm where the prostaglandins were discovered. Following his Ph.D. in prostaglandins in pregnancy he joined Pharmacia as a Scientist for drug development against Glaucoma. He had a key role as Study Director and main author on the studies on pharmacokinetics, metabolism, toxicokinetics and detection of Latanoprost/Xalatan and other prostaglandin analogues. XalatanR, a potent prostaglandin-based drug against Glaucoma registered world-wide in 1996 and sells over 1 billion US $ per year. After that he joined Uppsala University in 1996 where he devoted to research on Oxidative stress and inflammation in various diseases, specifically on isoprostanes and prostaglandins and their regulation.

Abstract:

Oxidative Stress and Inflammation, Department of Public Health. Faculty of Medicine, Uppsala University, Uppsala Science Park, SE-751 85 Uppsala, Sweden (samar.basu@pubcare.uu.se)

Arachidonic acid oxidation through free radicals and by cyclooxygenaes results in several short-lived unique bioactive compounds in the mammalian body namely, prostaglandins (PG) and isoprostanes. These eicosanoids are reliable parameters of oxidative stress and inflammation in addition to their vasoconstrictive, inflammatory and platelet-aggrigatory properties. Prostaglandin F2alpha (PGF2alpha) is a potent vasoconstrictory compound and is involved in various acute and chronic inflammation. 8-Iso-PGF2alpha, a major F2 -isoprostane evokes vasoconstriction in lung and kidney, and also serves as a reliable indicator of oxidative stress. By raising highly specific antibodies against 8-iso-PGF2alpha and PGF2alpha metabolite, we have investigated tissue injury and also their role in vivo. These methods have been successfully applied for studies of oxidative stress and inflammation and also drugs/antioxidants/radical scavengers treatment studies, namely experimental septic shock and acute inflammation, cardiopulmonary resuscitation (CPR) and brain injury after cardiac arrest, asthma, bone mineral density, cardiopulmonary bypass (CPB), pecutaneous coronary intervention (PCI) and angiography and several rheumatic diseases and risk factors of atherosclerosis. Rapid increase of these bioactive eicosanoids in experimental septic shock, CPR, CPB, PCI/angiography, and a higher levels of these parameters in patients with type 1 and type 2 diabetes, obesity, asthma, rheumatic diseases and smokers have seen in the body fluids with a distinct kinetics of appearance and disappearance, in addition to their regulation by various drugs and antioxidants. Thus, both isoprostanes and prostaglandins are involved in various diseases and riskfactors for atherosclerosis, and are potent target compounds to study oxidative stress and inflammation. In addition, these compounds have profound activities in physiology, like pregnancy which increases their novelty.

Short Curriculum Vitae

Young H. Ju, Ph.D.

Young H. Ju, Ph.D.
Rm 1121, CRC15, Virginia Tech
Blacksburg, VA 24060
Tele: 540-231-6168
Email: yhju@vt.edu

Professional Summary: 

In August, 2004, I have started my career as a tenure-track faculty in the Department of Human Nutrition, Foods and Exercise at Virginia Tech.  My major research interests are to identify bioactive food components that modify the breast cancer initiation and development, maximize efficacy and minimize adverse effects of dietary compounds, and understand their underlying molecular mechanisms of action on breast cancer.

Abstract: 

After menopause, reductions in the ovarian production and circulating levels of estrogen cause many women to experience symptoms such as hot flashes and mood swings.  Hormone replacement therapy (HRT) is often prescribed to relieve these symptoms.  However, many women are choosing not to use HRT because of recent reports warning against possible detrimental effects of conventional HRT on estrogen-regulated diseases including breast cancer, ovarian cancer, heart disease, and dementia.  Estrogens derived from plants (isoflavones) have been promoted as natural alternatives to conventional HRT, and a dramatic increase in the consumption of isoflavone supplements and products enriched with isoflavones has been documented in postmenopausal women.  The sales of soy and soy components are approaching 4 billion dollars annually, and the levels of estrogenic dietary isoflavones consumed by older Americans are increasing dramatically, due to active marketing of their perceived and potential health benefits.  We have investigated effect of a soy isoflavone, genistein, on breast cancer development, and their interaction with prescription drugs used to treat breast cancer using pre-clinical breast cancer models.  We have found detrimental effects of genistein; genistein at physiological concentrations stimulates the growth of estrogen receptor (ER) positive human breast cancer cells in vitro and in vivo; genistein negates the inhibitory effects of tamoxifen (an ER antagonist) and letrozole (an aromatase inhibitor) on the growth of ER(+) human breast cancer cells in vitro and in vivo; long-term dietary genistein exposure accelerates the progression of estrogen- and antiestrogen-responsive breast tumors to estrogen-insensitive breast tumors; and genistein-induced estrogen-insensitive tumors are able to grow aggressively without genistein supplementation.  Results from these studies raise concerns about the consumption of genistein-containing products by postmenopausal women with breast cancer. 

Education:

Positions and Honors:

Selected peer-reviewed publications (in chronological order):

1. Ju, Y.H. and Plewa, M.J. 1997. The plant-activation of the bicyclic aromatic amines benzidine and 4-aminobiphenyl. Environ. Mol. Mutagenesis 29:81-90.
   
2. Ju, Y.H. and Plewa, M.J. 1997. Involvement of nitoreductase and O-acetyltransferase on the mutagenicity of plant-activated benzidine and 4-aminobiphenyl. Environ. Mol. Mutagenesis. 30:330-338.
   
3. Ju, Y.H., Carson, K., Sun, J., Pathak D., Katzenellenbogen, B.S., Katzenellenbogen, J.A., and Helferich, W.G. 2000 Estrogenic Effects of Extracts from Cabbage, Fermented cabbage, and Acidified Brussel Sprouts on Growth of Estrogen-Dependent (MCF-7) and -Independent (MDA 231) Human Breast Cancer cells. J. Agric. Food Chem. 48 (10):4628-4634.
   
4. Allred, C.D., Allred, K.F., Ju, Y.H., Virant, S.M., and Helferich, W.G. 2001 Soy diets containing varying amounts of genistein stimulate growth of estrogen-dependent tumors in a dose dependent manner. Cancer Research 61(13):5045-5050.
   
5. Allred C.D., Ju Y.H., Allred, K.F., Chang, J.S., and Helferich, W.G. 2001 Dietary genistin stimulates growth of estrogen-dependent breast cancer tumors similar to that observed with genistein. Carcinogenesis 22:1667-1673.
   
6. Ju, Y.H., Allred, C.D., Allred, K.F., Karko, K.L., Doerge, D.R., and Helferich, W.G. 2001 Physiological Concentrations of Dietary Genistein Dose-dependently Stimulate Growth of Estrogen-dependent Human Breast Cancer (MCF-7) Tumor Implanted in Athymic Nude Mice. J. Nutr. 131(11):2957-2962.
   
7. Ju, Y.H., Doerge, D.R., Allred, K.F., Allred, C.D., and Helferich, W.G. 2002 Dietary genistein negates the inhibitory effect of tamoxifen on growth of estrogen-dependent human breast cancer (MCF-7) cells implanted in athymic mice. Cancer Research 62:2474-2477.
   
8. Ju, Y.H and Plewa, M.J. 2003 Mutant spectra analysis at hisG46 in Salmonella typhimurium strain YG1029 induced by mammalian S9- and plant-activated aromatic amines. Teratogenesis, Carcinogenesis and Mutagenesis 23:47-60.
   
9. Allred, C.A., Allred, K. F., Ju, Y.H., Doerge, D.R., Schantz, S., Korol, D., and Helferich, W. G. 2004 Dietary Genistein Results in Larger MNU-induced, Estrogen-dependent Mammary Tumors Following Ovariectomy of Sprague-Dawley Rats. Carcinogenesis 25:211-218.
10. Muthyala, R.S., Ju, Y.H., Sheng, S., Williams, L.D., Doerge, D.R., Helferich, W.G., and Katzenellenbogen, J.A. 2004 Equol, a Natural Estrogenic Metabolite from Soy Isoflavones: Convenient Synthesi

Heather F. Smith, Ph.D.

Heather F. Smith, Ph.D.
Department of Basic Medical Sciences,
University of Arizona, College of Medicine- Phoenix
425 N. 5th St.
Phoenix, AZ 85004-2157
Tel: (480)965-9037 (office)
Email:  hfsmith2@email.arizona.edu

Abstract: 

As different functional and developmental modules (FDMs) of the skull in humans and other primates experience different loading regimes, patterns of ossification, and ontogenetic trajectories, it is likely that they will reflect phylogenetic information differentially and evolve according to different processes. The three-dimensional morphology of crania from a wide range of geographically dispersed populations were compared to molecular data and environmental variables to determine which FDMs are most informative about population history in humans. It was determined that the endochondrally ossifying basicranium and temporal bone reflected genetic distance most reliably, followed by the upper facial skeleton, dentition, and mandible. The morphology of the neurocranium, and the high strain masticatory regions of the facial skeleton, however, exhibited extensive plasticity. An investigation of climatic variables revealed a correlation between cranial size and mean annual temperature, and that temporal bone shape is evolving under an isolation by distance model. An investigation using papionin (baboon) primates found that their cranial morphology is characterized by allometry, or size-related shape changes.  Finally, a comparison of temporal bone morphology in Neandertals, Anatomically Modern Humans, and modern human populations indicated a distant relationship between Neandertals and modern humans, supporting an Out of Africa model for modern human origins.

Education:

Positions and Honors:

Selected peer-reviewed publications (in chronological order):

1. Videan, E.N., Fritz, J., Murphy, J., Borman, R., Smith, H.F., Howell, S. (2005). Training captive chimpanzees to cooperate for an anesthetic injection. Lab Animal 34(5):43-48.
   
2. Videan, E.N., Fritz, J., Schwandt, M., Smith, H.F., Howell, S. (2005). Controllability in environmental enrichment for captive chimpanzees (Pan troglodytes). Journal of Applied Animal Welfare Science 8:117-130.
   
3. El-zaatari, S., Grine, F.E., Teaford, M.,  Smith, H.F. (2005). Molar microwear and dietary reconstructions of fossil cercopithecoidea from the Plio-Pleistocene deposits of South Africa. Journal of Human Evolution 49:180-205.
   
4. Grine, F.E., Spencer, M.A., Demes, B., Smith, H.F., Strait, D.S., Constant, D. (2005). Molar enamel thickness in the chacma baboon, Papio ursinus (Kerr 1792). American Journal of Physical Anthropology 128:812-822.
   
5. Mittra, E.S., Smith, H.F., Lemelin, P., Jungers, W.L (2007). Comparative morphometrics of the primate apical tuft. American Journal of Physical Anthropology 134:449-459.
   
6. Smith, H.F., Terhune, C.E., Lockwood, C.A. (2007). Genetic, geographic, and environmental correlates of human temporal bone variation. American Journal of Physical Anthropology 134:312-322.
   
7. Smith, H.F., Grine, F.E. (2008). A cladistic analysis of early Homo crania from Sterkfontein and Swartkrans, South Africa. Journal of Human Evolution 54:684-704.
   
8. Grine, F.E., Smith, H.F., Heesy, C.P., Smith, E. (in press). Affinities of the Homo fossils from Swartkrans, Sterkfontein and Drimolen, South Africa: phenetic evidence from molar cusp proportions. In: Grine, F.E., Leakey, R.E., Fleagle, J.G. (Eds.), The first humans: origins of the genus Homo.
   
9. Smith, H.F. (2009). Which cranial regions reflect genetic distances most reliably in humans? Evidence from three-dimensional morphology. American Journal of Human Biology 21:36-47.
   
10. Smith, H.F., Fisher, R.E., Everett, M.L., Bollinger, R.R., Parker, W. (in review). The evolution and function of the mammalian appendix. BMC Evolutionary Biology
    
11. Fisher, R.E., Smith, H.F., Goldstein, B. (in prep). Anatomy and biomechanics of the spine. Invited chapter in: Kirshblum, S., Campagnolo D. (Eds), Spinal Cord Medicine. 2nd edition. Lippincott Williams and Wilkins.

Research Projects Ongoing or Completed During the Last 3 Years:

“Doctoral Dissertation Improvement: A comparison of human population distances using genetic and craniometric data.”
Funding source: National Science Foundation (BCS-0622570)
Principal Investigator: Mark A. Spencer
Co-PI: Heather F. Smith
Period: September 6, 2006 to August 31, 2007

and

Funding source: The Wenner-Gren Foundation (#7499)
Principal Investigator: Heather F. Smith
Period: July 1, 2006 to July 1, 2007
The objective of this project was to assess the correspondence between genetic distances and the 3D morphology of several cranial regions in humans, and to contribute to a greater understanding of
the phenotype-genotype relationship in this species.

“A primate catarhine primate inference model for hominin morphological evolution.”
Funding source: L.S.B. Leakey Foundation
Principal Investigator: Heather F. Smith
Period: February 1, 2009 to June 30, 2010
The objective of this project is to assess the degree of phylogenetic utility of the landmark-based morphology of specific anatomical regions of the skull and functional and developmental modules in catarhine primates, and reveal which aspects of morphology are most appropriate for phylogenetic reconstructions of fossil hominin taxa.

Teaching Experience: 

Classes co-taught as post-doctoral associate

Graduate teaching assistant positions

Summary: 

Dr. Heather Smith is a postdoctoral research associate in the College of Medicine at the University of Arizona. Her current postdoctoral research projects include an investigation of paraspinal muscular defects in Notch signaling pathway mutant mice, and a comparative anatomical study of the mammalian cecal appendix. Her independent research, starting with her Ph.D. dissertation, has focused on the genetic and epigenetic factors contributing to differences in cranial morphology across primates, and the evolution of current patterns of cranial variation. In addition to conducting her research, Dr. Smith currently co-teaches a dissection-based gross anatomy course for first-year medical students at the University of Arizona.

Dr. Smith completed a Bachelors’ degree in Biological Anthropology at Arizona State University’s Barrett Honors College in 2001, and a Masters’ degree in Biological Anthropology from Stony Brook University in 2003. She returned to Arizona State to complete her Ph.D. in Biological Anthropology, which she was awarded in May 2008. Her dissertation research on human cranial morphology and evolution was supported by grants from the National Science Foundation and the Wenner-Gren Foundation for Anthropological Research.

John A. Anstrom, Ph. D.

"Histological Development of Cerebral Vessels in Human Neonates Born Prematurely: Relation to Germinal Matrix Hemorrhage"

John A. Anstrom, Ph. D.
Adjunct Assistant Professor
Biology Department
Young Harris College
Young Harris, GA
Tel: (706) 379-5352  (office)
(336) 391-4946 (cell)
Email: jaanstrom@yhc.edu

Abstract:

Approximately 10% of all births in the US are premature. Neonates born prematurely are at risk for hemorrhage in the germinal matrix, a collection of neuronal precursor cells present in the subventricular zone of the brain until 38 weeks gestation.  The etiology of germinal matrix hemorrhage is complex and involves blood flow dynamics, factors intrinsic to the blood vessel wall, as well as factors extrinsic to the wall such as the association between brain vessels and glial end-feet. We have carried out autopsy studies using brain from neonates born live during the third trimester and died within the first few hours or days following birth to assess the developmental status of brain vessels. Using immunohistochemistry, structural components in the wall of germinal matrix vessels were compared to similarly prepared vessels in other brain regions where hemorrhage is not frequent. Capillaries in the germinal matrix exhibit an accumulation of collagen IV, a major structural protein of the basement membrane, equivalent to that displayed by vessels in other brain areas indicating that the vessel wall does not lack in this extracellular component and therefore, hemorrhage is not related to an absence of intrinsic structural support.  Germinal matrix vessels do however, exhibit differences in the accumulation of blood-brain barrier components when compared to vessels in other brain regions. We hypothesize that endothelial cells of germinal matrix vessels are slow to accumulate the proteins of tight junctions that are the structural basis of the blood-brain barrier. An incomplete and weak connection between adjacent endothelial cells, related to a paucity of tight junction proteins, may leave these vessels particularly susceptible to the underlying systemic factors that lead to vascular rupture.

Education:

Professional Experience:

Teaching Experience:

Research Experience:

Interests:

Cell biological nature of embryogenesis: I have used sea urchin embryos to study the transformation of embryonic epithelial cells into migratory mesenchymal cells.

Cerebral vascular development and pathology: I have studied the anatomical maturation of cerebral blood vessels in human neonates at ages corresponding to the third trimester and have related the results to germinal matrix hemorrhage—a significant medical problem that afflicts babies born prematurely.

Grant History:

Intramural Research Support
3 awards for a total of $17,000
to pursue studies related to morphogenesis
John A. Anstrom, Ph.D. principal investigator

March of Dimes Birth Defects Foundation (Basil O'Connor Starter Scholar Research Award); 10/1/1988 - 9/31/1991; $75,000
The regulation of primary mesenchyme cell migration in sea urchin embryos (yr 1 = $30,000; yr 2 = $30,000; yr 3 = $15,000 [extended year])
John A. Anstrom, Ph.D. principal investigator

Selected Recent Publications:

1. Anstrom JA, Thore CR, Moody DM, Challa VR, Block SM, Brown WR. Morphometric assessment of collagen accumulation in germinal matrix vessels of premature human neonates. Neuropathol Appl Neurobiol 2005; 31:181-190.
2. Anstrom JA, Moody DM, Thore CR, Challa VR, Block SM, Brown WR. Histological analysis of vascular patterns and connections in the germinal matrix of premature neonates. Neuroembryol 2005; 3:4-12.
3. Anstrom JA, Thore CR, Moody DM, Challa VR, Block SM, Brown WR. Germinal matrix cells associate with veins and a glial scaffold in the human fetal brain. Dev Brain Res 2005; 160:96-100.
4. Anstrom JA, Thore CR, Moody DM, Brown WR. Immunolocalization of tight junction proteins in blood vessels in human germinal matrix and cortex. Histochem Cell Biol 2007; 127:205-213.
5. Thore CR, Anstrom JA, Moody DM, Challa VR, Marion MC, Brown WR. Morphometric analysis of arteriolar tortuosity in human cerebral white matter of preterm, young, and aged subjects. J Neuropathol Exp Neurol 2007; 66:337-345.

Professional Summary:

I received my BS degree in Biology from the Pennsylvania State University and PhD degree in Anatomical Sciences from the State University of New York at Buffalo. I went on to Indiana University where I worked in the laboratory of Dr. Rudolf Raff, a developmental biologist. My work in Dr. Raff’s lab contributed to the discovery of histone messenger RNAs that are stored exclusively in the pronucleus of an unfertilized oocyte until their release at fertilization. I also used immuno-electron microscopy to describe the distribution of a cell surface glycoprotein that appears on mesenchymal cell precursors of the larval skeleton. Following my move from Indiana University to Wake Forest University School of Medicine (known at the time as The Bowman Gray School of Medicine) I continued my microscopic studies of sea urchin embryonic mesenchymal cells, using this system as a means to understand epithelial-mesenchymal transformations as they occur in most embryos including humans. In 1998 I changed my emphasis and began to apply my microscopic methods to the development of cerebral blood vessels in the human brain. This work was in collaboration with Dr. Dixon Moody of the Department of Radiology at Wake Forest University School of Medicine. Several of our articles described structural aspects of vessels in the subventricular area of the brain of neonates born prematurely and have assessed how vessel wall structure might influence the development of hemorrhage in this special population of newborns.