Digital Commons Network^™

Genome Announcement For E Cluster Phage Tarkin, Katherine Cleary

Chemistry & Biochemistry Student Scholarship

Katherine Cleary ’23
Major: Biochemistry
Faculty Mentor: Dr. Kathleen Cornely, Chemistry and Biochemistry

Purification And Kinetic Characterization Of Mutant R111v Human Cytosolic Malate Dehydrogenase, Jackson Demartino

Chemistry & Biochemistry Student Scholarship

Metabolic profiling for a variety of cancerous cells indicate significant increases in the levels of glucose consumption. To support uncontrolled cell division, cancer cells also present an uncoupling of glycolysis from the citric acid cycle to promote glucose carbons to the synthesis of biomass, therefore, requiring a constant supply of NAD⁺. Recent studies indicate that cancer cells exhibit upregulated cytosolic malate dehydrogenase (MDH1) activity, which catalyzes the conversion of oxaloacetate to malate with the oxidation of NADH, generating NAD⁺. Given its increased activity, MDH1 may serve as a valuable target for treating cancer. Here we report …

Exploring Indicator Displacement Assays For Phosphate Detection In Seawater, Francis Radics

Chemistry & Biochemistry Student Scholarship

Francis Radics ’22
Major: Biochemistry
Faculty Mentor: Dr. John Breen, Chemistry and Biochemistry

Indicator displacement assays are based on the optical signal modulation of a noncovalently bound indicator upon dissociation by an analyte species. Our work has focused on exploring the lower detection limits for luminescent displacement assays for inorganic phosphate in seawater using complex ions containing two di(2-picolyl)amine ligands (also called DPA or bis(2-pyridylmethyl)amine), each coordinating a zinc cation. Following the work of B.D. Smith and coworkers, we have prepared three ligands by covalently attaching two DPA moieties, 2,6-bis(chloromethyl) benzene, and 2,6-bis(chloromethyl)-4-methylphenol, and 1,2-phenylenedimethylamine, for assays with 6,7-dihydroxy-4-methanesulfonic acid …

Development And Kinetic Survey Of A G148t Mutant Human Cytosolic Malate Dehydrogenase Isoform 3 Enzyme With Oxaloacetate And A-Ketoglutarate, Ethan N. Dionne

Chemistry & Biochemistry Student Scholarship

Cancer cells often use an altered metabolic pathway in which glycolysis, uncoupled from the citric acid cycle, serves as the primary source of ATP. To support cancer cell proliferation and growth, the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) must have a constant source of NAD. While lactate dehydrogenase (LDH) in its conversion of pyruvate to lactate is a well-known source of cytosolic NAD for GAPDH activity, cytosolic malate dehydrogenase (MDH1) also plays a role in cell proliferation through its generation of cytosolic NAD by the conversion of OAA to malate. This development has implicated MDH1 in cancer cell metabolism and characterizing …

Proline To Serine Mutation In The Active Site Loop Of Malate Dehydrogenase Alters Substrate Specificity, Olivia J. Schmitt

Chemistry & Biochemistry Student Scholarship

Cancer cells preferentially undergo glycolysis in aerobic environments, a phenomenon termed the Warburg effect. Malate dehydrogenase (MDH) catalyzes the reversible interconversion of malate and oxaloacetate. Human cytosolic malate dehydrogenase (hMDH1) isoform 3 is involved in the malate-aspartate shuttle (MAS), which oxidizes cytosolic NADH. hMDH1 is implicated in high aerobic glycolysis in cancer cells because NAD is a necessary cofactor for glycolysis. Thus, hMDH1 is a promising molecular target for cancer treatment. A single proline residue at position 110 in the mobile active site loop of hMDH1 was mutated to a serine with the intention of altering the enzyme’s substrate specificity. …

An Investigation Of K2 Mycobacteriophage Lysin A Proteins, Ethan Dionne

Chemistry & Biochemistry Student Scholarship

Major: Biochemistry
Faculty Mentor: Dr. Kathleen Cornely, Chemistry and Biochemistry

Towards The Development Of Low-Cost And Easily-Deployable Sensing Platforms For Phosphate, Maureen Pontarelli, Thomas Koch

Chemistry & Biochemistry Student Scholarship

Maureen Pontarelli ’20
Major: Chemistry

Thomas Koch '20
Major: Biochemistry

Faculty Mentor: Dr. John Breen, Chemistry and Biochemistry

Ile126his And Lys129his Surface Mutations Aid In Purification Of Haemophilus Influenzae Carbonic Anhydrase Through Increased Metal Ion Affinity, Timothy Rigdon, Kathleen Cornely

Chemistry & Biochemistry Student Scholarship

Carbonic anhydrase (CA) is an enzyme that plays a major role in the survival of many bacterial, chiefly Haemophilus influenzae. Because of its crucial role in bacteria, recent research has turned to CA as a possible target for drug development to kill bacteria and possibly cure different bacterial diseases. While research has focused on this drug target, the isolation and purification of specific types of CA has remained a major obstacle for further research. The current method of immobilized metal affinity chromatography (IMAC) with a Ni-NTA column is used widely for CA purification; however, the H. influenzae carbonic anhydrase …

Hepatic Lipase Treatment Of Chylomicron Remnants Increases Exposure Of Apolipoprotein E, Dawn L. Brasaemle, Kathleen Cornely-Moss, André Bensadoun

Chemistry & Biochemistry Faculty Publications

The consequences of hepatic lipase treatment of chylomicron remnants were studied. Rats were fed corn oil to induce production and secretion of chylomicrons and were then injected with polyclonal antiserum raised against hepatic lipase to specifically and quantitatively inhibit hepatic lipase activity in vivo. A fraction enriched in chylomicron remnants was isolated from rat plasma by a brief centrifugation step that preferentially isolates triglyceride-rich apolipoprotein (apo) B-48-containing lipoproteins. The chylomicron remnants were then treated with hepatic lipase in vitro, or incubated under identical conditions in the absence of enzyme (control incubations). Hepatic lipase-treated and control chylomicron remnants were isolated by …