The Zdilla Lab is involved in research aiming to produce new clinical measurements and discover new links between human structure and function.

• A novel method of assessing zinc nutriture: (Starkey, Saling, Basil)
  A new, noninvasive, method of assessing the adequacy/inadequacy of zinc nutrition based on the taste perception of zinc is being developed.  The implications of the new clinical measurement technique are wide-ranging from gaining insight into immune function and reproductive function to predicting predispositions to cavities, anorexia, and problems with brain function.
• Correlating salivary carbonic anhydrase VI (gustin) with zinc taste perception and immunity: (Starkey)
  An enzyme in saliva known as “gustin” may have a great influence over how we taste metals, such as zinc.  It also plays a role in the pH balance of our oral cavity.  The enzyme may also be a window into our immune function.  We are measuring gustin concentrations in saliva and exploring its correlations with human health.
• Circumvallate papillae characteristics and zinc taste perception: (Hunt, Gibson)
  Taste buds, the small structures that house our taste receptors are located, predominantly, in organs called papillae.  We are using endoscopy and intraoral photography to view circumvallate papillae located at the far back of the tongue in order to learn more about how their characteristics are related to our ability to taste zinc.
• Fungiform papillae characteristics and zinc taste perception: (Quikel, Dennis)
  Fungiform papillae are organs located, chiefly, at the tip of the tongue.  These organs house taste buds.  We are analyzing the density and physical characteristics of these papillae to explore their relationship with the ability to taste zinc.

Student Researchers:

• Leah Starkey - Senior, Majors: Biology and Chemistry, Pre-Med
• Julia Saling - Senior, Majors: Biology and Chemistry, Pre-Med
• Alicia Hunt - Senior, Major: Dental Hygiene
• Laken Gibson - Senior, Majors: Biology and Exercise Physiology, Pre-Dental
• Kurtis Dennis - Sophomore, Major: Biology, Pre-Dental
• Lauren Quickel - Freshman, Major: Nursing

Matthew Zdilla’s Faculty Page

Zachary Loughman

Research in my lab focuses on crayfish natural history, taxonomy, and conservation biology, with an emphasis on crayfishes that occur in West Virginia. To do this, myself and West Liberty University Biology students travel throughout West Virginia and the southeastern United States surveying crayfishes. The ultimate goal of this research is elucidating the natural history of these enigmatic animals. By understanding distribution and potential environmental threats to crayfishes, conservation recommendations and actions ultimately will be more useful and efficient.  In addition to this work, we study the ecology of high elevation burrowing crayfishes, investigate the systematics of the Cambarus robustus complex, and maintain the West Liberty University Astacology Collection which currently houses 1,500 lots of catalogued crayfishes from across West Virginia and the southeastern United States.

Zachary Loughman’s Faculty Page

Publications:

Journal Articles

Loughman, Z. J., S. A. Welsh, and T. P Simon. 2012. Occupancy rates of primary burrowing crayfish in natural and disturbed large river bottomlands. Journal of Crustacean Biology. 32(4): 557-564.

Loughman Z.J. and T. P. Simon. 2011. Zoogeography, taxonomy, and conservation of West Virginia’s Ohio River floodplain crayfishes (Decapoda, Cambaridae). ZooKeys 73: 1–78.

Loughman, Z. J., T. P. Simon and S. A. Welsh. 2011. Cambarus (Puncticambarus) smilax, a new species of crayfish (Crustacea; Decapoda: Cambaridae) from the Greenbrier River basin of West Virginia. Proceedings of the Biological Society of Washington. 124:2, 84-99.

Loughman, Z. J., N. Garrison, S. A. Welsh, and T. P. Simon. Zoogeography, conservation, and ecology of crayfishes within the Cheat River basin of the upper Monongahela River drainage, West Virginia.  West Virginia Academy of Sciences. 2010.

Loughman, Z. J. 2010. Forward to Conservation, ecology, and biology of North American Crayfishes. Southeastern Naturalist 9 (Special Publication 3): 1-11.

Loughman, Z. J. 2010. Ecology of Cambarus (J.) dubius in north Central West Virginia in Southeastern Naturalist 9 (Special Publication 3): 200-217.

Loughman, Z. J., 2009. Crayfishes of Western Maryland: conservation and natural history. Southeastern Naturalist 9 (Special Publication 3): 33-62.

Loughman, Z. J. and S. Welsh. 2009. Distribution and conservation standing of West Virginia crayfishes. Southeastern Naturalist 9 (Special Publication 3): 63-78.

Welsh, S. A., Z. J. Loughman, T. P. Simon. 2010. Concluding remarks: A symposium on the conservation, biology, and natural history of the crayfishes of the southeastern United States. Southeastern Naturalist 9 (Special Publication 3): 267-269.

Loughman, Z. J., T. P. Simon, S. Welsh. West Virginia crayfishes: observations on distribution, natural history, and conservation. North Eastern Naturalist. 16 (2): 225-238.

Loughman, Z. J. and J. W. Reid. 2009. Crayfishes (Crustacea:Decapoda) and copepods (Crustacea:Copepoda) of Potomac Gorge National Park, Virginia. Banisteria 31: 30-37.

Loughman, Z. J., 2007.  Cambarus (T.) thomai in Maryland: conservation implications of an introduced burrowing crayfish population. Freshwater Crayfish News. 29 (3) (Cover Article)

Loughman, Z. J., 2007. First record of Procambarus (O.) acutus (White River Crayfish) in West Virginia with notes on its natural history. Northeastern Naturalist. 14 (3) p. 495-500

Books

Loughman, Z. J., S. A. Welsh, and T. P. Simon. 2010. Conservation, Biology, and Natural History of Crayfishes from the Southern United States: Proceedings of a 2008 Symposium of the Southern Division of the American Fisheries Society. Southeastern Naturalist. Special Publication #3.

Fuhua Chen

Analysis of tissue volumes in human brains, and its relation to some diseases based on magnetic-resonance-imaging (MRI) image processing

It has been widely recognized that by tracing and analyzing the change of the volumes of different tissues in human brains, some brain-related diseases can be found earlier so that some measure can be taken to stop the disease at its early stage. For example, it’s found that Alzheimer, a kind of intelligence disease for senior people, is currently very hard to cure. In many cases, doctors can only stop or slow the development of the disease. Now more and more doctors believe that Alzheimer has something to do with the shrink of some tissues (also called matters) in human brains. Therefore, by comparing the change of the volumes of different matters in a human brain, potential Alzheimer can be found at its very early stage, and so can be stopped or cured easily.

Since it is impossible for doctors to dissect human brains to estimate the volumes of different tissues, a feasible way is to use advanced brain imaging techniques to obtain brain images, with which the volumes of different matters can be estimated using image processing methods. The key step to estimate tissues’ volumes with images is image segmentation, i.e., partitioning an image into several different areas based on the voxel/pixel’s feature such that voxels/pixels with same or similar features are classified to a same class or area. Currently, magnetic-resonance-imaging (MRI) is an economic way with less injury to human health comparing with other imaging techniques such as computed tomography (CT), ultrasound imaging (UI) and positron emission tomography (PET). However, there are two shortcomings of MRI which prevent from obtaining precise segmentation. One is partial volume, which has been extensively studied in recent decade; another is so-called central-gray-matter (also called deep-gray-matter) which intensities (features) are very close to white matter making hard to distinguish between white matter and central-gray-matter. Therefore, an efficient segmentation method is essential to obtain precise estimation of volumes of different matters.  The main goal of this project is to develop advanced models and/or algorithms to efficiently segment MRI brain images.

A three-dimensional MRI brain image usually contains 240 slices (1mm thick) of two-dimensional images. Figure 1 shows what the white matter is and what the gray matter is.

Figure 1

With a set of two-dimensional images, the first step is to remove the skull from the images, then to remove the cerebellum because only cerebrum is needed to calculate. These two steps are shown in Figure 2 from left to right. The right picture contains two different pieces of the MRI brain images. The middle ones are the images with the skull removed, and the right ones are the images with both skull and cerebellum removed.

Figure 2

After the pure cerebrum is obtained, an advanced model or algorithm can be applied to those images. Different matters can then be separated, called segmentation. Figure 3 is an example of such a result, where bounded by white contours is the white matter, bounded by the green contour is the gray matter, and bounded by the red contour is the cerebrospinal fluid (CSF).

Figure 3

Fuhua Chen’s Faculty Page

Joseph Horzempa

Francisella tularensis is a highly infectious microorganism with fewer than 10 inhaled bacteria causing the fatal disease tularemia.  This bacterium has been weaponized and could be used for bioterrorism, prompting the Center for Disease Control and Prevention to classify F. tularensis as a Category A biodefense agent.  In addition to the threat of an intentional release, F. tularensis causes a variety of naturally occurring human infections that can be acquired by inhalation, arthropod bites, oropharyngeal exposure, or by contact.  My long term goals involve understanding the pathogenesis, persistence, and transmission, of F. tularensis.  Ultimately, I am interested in identifying novel therapeutics to combat this pathogen and other bacterial pathogens.

The virulence of F. tularensis has principally been associated with this organism’s ability to replicate within phagocytic cells of the innate immune system, such as macrophages. In addition to macrophages, F. tularensis can invade and replicate in a range of non-phagocytic host cells such as alveolar epithelial cells, kidney epithelial cells, hepatocytes, and fibroblasts. F. tularensis also employs mechanisms to suppress the host innate immune response, resist complement, and inhibit macrophage and neutrophil effector functions. The ability of F. tularensis to detect and respond to environmental signals contributes to this organism’s success as a pathogen. My work has shown that mammalian temperature modulates virulence gene expression. Differential responses to temperature by F. tularensis, as determined by microarray analysis, provided a focused list of relevant candidate virulence determinants to investigate further.  These virulence factors will be primary therapeutic targets.

Uptake of F. tularensis into both macrophages and non-phagocytes is mediated by the host cell’s endocytic machinery.  Recently, I made the observation that Francisella also invades erythrocytes during infection – cells incapable of endocytosis.  A focus of my research program involves examination of the molecular mechanisms facilitating erythrocyte invasion by F. tularensis and the biological role of this phenomenon.  Both erythrocyte and bacterial factors will be investigated for their contribution toward invasion.  To elucidate the biological role of erythrocyte invasion, I intend to investigate whether erythrocyte invasion contributes to the pathogenesis of F. tularensis.   Because erythrocytes are long-lived cells, I will also explore a role in disease persistence for invasion of red blood cells.  Other pathogenic bacteria that invade erythrocytes do so to enhance transmission by arthropod vectors, such as ticks.  Therefore, I will examine a role in enhancing arthropod transmission.  Furthermore, I have established collaborations that will allow me to examine clinical specimens from tularemia patients to assess the level of erythrocyte invasion during human infection.  The information generated in these studies will enhance our understanding of this pathogen’s biology during different stages of infection.  Also, by understanding how the erythrocyte is manipulated to allow F. tularensis access to its intracellular space, we will gain insight into the cell biology of red blood cells.

My research agenda also involves investigating the pathogenesis of the opportunistic pathogen, Pseudomonas aeruginosa.  In addition, I am developing and characterizing a novel live vaccine platform that can be engineered to elicit protection against a variety of bacterial pathogens including P. aeruginosa.

Joseph Horzempa’s Faculty Page

Publications

 Russo, B.C., J. Horzempa, D.M. O’Dee, D.M. Schmitt, M.J. Brown, P.E. Carlson Jr., R.J. Xavier, and G.J. Nau.  2011. A Francisella tularensis locus required for spermine responsiveness is necessary for virulence. Infect. Immun.  In press.

Horzempa, J., D.M. O’Dee, D.B. Stolz, J.M. Franks, D. Clay, and G.J. Nau. 2011.  Invasion of erythrocytes by Francisella tularensis.  J. Infect. Dis. 204: 51-59.

Editorial commentary by J. Wayne Conlan. 2011. Francisella tularensis: A Red-blooded Pathogen. J. Infect. Dis. 204: 6-8

Kalivoda, E.J., J. Horzempa, N.A. Stella, A. Sadaf, R.P. Kowalski, G.J. Nau, and R.M.Q. Shanks. 2011. New vector tools with a hygromycin resistance marker for use with opportunistic pathogens. Mol. Biotechnol. 48:7-14

Qutyan, M., M. Henkel, J. Horzempa, M. Quinn, and P. Castric. 2010. Glycosylation of pilin and nonpilin protein constructs by Pseudomonas aeruginosa 1244. J. Bacteriol. 192:5972-81.

Horzempa, J., D.M. O’Dee, R.M.Q. Shanks, and G.J. Nau. 2010. Francisella tularensis ΔpyrF mutants show that replication in non-macrophages is sufficient for pathogenesis in vivo. Infect. Immun. 78:2607-19.

Horzempa, J., R.M.Q. Shanks, M.J. Brown, B.C. Russo, D.M. O’Dee, and G.J. Nau. 2010. Utilization of an unstable plasmid and the I-SceI endonuclease to generate routine markerless deletion mutants in Francisella tularensis. J. Microbiol. Methods. 80:106-8

Carlson Jr., P.E.*, J. Horzempa*, D. M. O’Dee*, C.M. Robinson, P. Neophytou, A. Labrinidis, and G.J. Nau. 2009. Global transcriptional response to spermine, a component of the intra-macrophage environment, reveals regulation of Francisella gene expression through insertion sequence elements. J. Bacteriol. 191:6855-64. *These authors contributed equally to this work.

Horzempa, J., P.E. Carlson Jr., D.M. O’Dee, R.M.Q. Shanks, and G.J. Nau. 2008. Global transcriptional response to mammalian temperature provides new insight into Francisella tularensis pathogenesis.  BMC Microbiol. 8:172.

Horzempa, J., T.K. Held, A.S. Cross, D. Furst, M. Qutyan, A.N. Neely, and P. Castric.  2008.  Immunization with Pseudomonas aeruginosa 1244 pilin provides O-antigen-specific protection.  Clin. Vaccine Immunol. 15:590-597.

Horzempa, J., D.M. Tarwacki, P.E. Carlson, Jr., C.M. Robinson, and G.J. Nau. 2008. Characterization and application of a glucose-repressible promoter in Francisella tularensis.   Appl. Environ. Microbiol. 74:2161-2170.

Horzempa, J., C. Dean, J. Goldberg, and P. Castric. 2006. Pseudomonas aeruginosa 1244 pilin glycosylation: glycan substrate recognition. J. Bacteriol. 188:4244-52.

Horzempa, J., J. E. Comer J.E., S. A. Davis, and P.A. Castric. 2006. Glycosylation substrate specificity of Pseudomonas aeruginosa 1244 pilin. J. Biol. Chem. 281:1128-1136.

Smedley, J.G., III*, E. Jewell*, J. Roguskie*, J. Horzempa*, A. Seyboldt, D. B. Stolz, and P. Castric. 2005. Influence of pilin glycosylation on Pseudomonas aeruginosa 1244 pilus function. Infect. Immun. 73:7922-7931. *These authors contributed equally to this work.