@inproceedings{materials mediated cellular engineering: how does it work?_2024, booktitle={Immunoengineering Gordon Research Conference}, year={2024}, month={Feb} }
 @inproceedings{drydux: a biomaterial platform for robust, inexpensive car t cell generation_2023, booktitle={Biomaterials Gordon Research Conference}, year={2023}, month={Jun} }
 @inproceedings{drydux: an implantable technology for rapid, inexpensive, potent car t therapy_2023, booktitle={15th Annual Bioprocessing Summit}, year={2023}, month={Aug} }
 @inproceedings{mallory_xu_schiermeyer_gildea_felder_2019, title={Abstract P3033: Sodium Induced Dopamine D1 Receptor (D1R) Plasma Membrane Recruitment Involves Protein Phosphatase 2a (PP2A) and Aminopeptidase N (APN)}, url={http://dx.doi.org/10.1161/hyp.74.suppl_1.p3033}, DOI={10.1161/hyp.74.suppl_1.p3033}, abstractNote={
            The cooperative relationship between the dopamine type 1 receptor (D
            1
            R) and the angiotensin type 2 receptor (AT
            2
            R) signaling pathway in renal proximal tubule cells (RPTCs) is known as a significant mediator of natriuresis and systemic sodium (Na
            +
            ) homeostasis. The degree of Na+ induced D
            1
            R plasma membrane recruitment correlates with the degree of salt sensitivity of blood pressure in urine-derived RPTCs collected from clinical study participants. We recently published that the Protein Phosphatase 2A (PP2A) pathway is a common and necessary pathway for D
            1
            R and AT
            2
            R cooperativity and function. Here, we extend these studies by examining the autocrine signaling in previously published model RPTCs that are normally D
            1
            R cAMP coupled (i22) and D
            1
            R cAMP uncoupled (i19). D
            1
            R and aminopeptidase N (APN) plasma membrane expression was measured by flow cytometry, and an elevated NaCl solution (PBS + 50 mM NaCl, 1 hour) was used for increased salt exposure. The addition of FTY720 (2.5 μM, 1 hour) activated PP2A. Normally coupled i22 cells in the presence of increased Na
            +
            significantly increase plasma membrane D
            1
            R (1.41±0.10 fold vs VEH, n=3 p<0.05), but uncoupled i19 cells did not. FTY720 alone did not significantly increase plasma membrane D
            1
            R in uncoupled i19 cells; however, FTY720 along with increased Na
            +
            did significantly increase i19 plasma membrane D
            1
            R (1.61±0.17 fold vs VEH, n=9 p<0.001). In order to inhibit local production of dopamine, BCH (2-aminobicyclo(2,2,1)-heptane2-carboxylic acid, 1 mM), a LAT2 inhibitor, and Carbidopa (100 μM), a dopamine decarboxylase inhibitor, were used and completely blocked the plasma membrane recruitment of D
            1
            R. We next looked at enzymes involved in the regulation of AngIII peptide, the preferred agonist of the AT
            2
            R. APN is the enzyme that converts AngIII to AngIV. Under elevated Na
            +
            conditions levels of APN significantly decreased in normally coupled i22 but not in the uncoupled i19 cells (-7.3 ±0.01% vs VEH, n=6 p<0.01). In summary, the data presented suggests that PP2A and enzymes involved in the local production of dopamine and AngIII, may be involved in the Na+ induced plasma membrane recruitment of D
            1
            R.
          }, booktitle={Hypertension}, author={Mallory, Micah J and Xu, Peng and Schiermeyer, Katherine A and Gildea, John J and Felder, Robin A}, year={2019}, month={Sep} }
 @inproceedings{gildea_mallory_felder_2017, title={Abstract P320: Cooperative Signaling and Membrane Recruitment of the Dopamine-1 (D1R) and Angiotensin Type 2 (AT2R) Receptors in Human Renal Proximal Tubule Cells (RPTC)}, url={http://dx.doi.org/10.1161/hyp.70.suppl_1.p320}, DOI={10.1161/hyp.70.suppl_1.p320}, abstractNote={
            The D
            1
            R and AT
            2
            R are interdependent natriuretic receptors that are critical for the regulation of renal sodium balance and are implicated in both hypertension and salt-sensitivity. D
            1
            R and AT
            2
            R stimulation with the D
            1
            R agonist fenoldopam (FEN) and Angiotensin III (AngIII), selectively increases cAMP and cGMP, respectively, leading to D
            1
            R and AT
            2
            R recruitment to the cell surface (measured by fluorescent extracellular receptor epitope specific antibodies). The interdependence of the D
            1
            R and AT
            2
            R recruitment was investigated following AT
            2
            R stimulation with AngIII (10 nmol/L 1 hour) which leads to D
            1
            R cell surface recruitment using a normally D
            1
            R/Gs coupled cell line (i22) (VEH 8209±863, AngIII 19485±3425 RFU, n=6, p<0.05) but not in a D
            1
            R uncoupled from Gs cell line (i19). These data were verified by increasing intracellular sodium with monensin (100 μM, 1 hr) and measuring cell surface binding with a fluorescent labelled D
            1
            R agonist SKF83566 (10 nmol/L, 1 hr, i22 1.67±0.7 fold, n=5, p<0.0001, i19, NS). The importance of dopamine in regulating these receptor actions was shown by stimulating the AT
            2
            R with AngIII and measuring D
            1
            R recruitment followed by blockade of amino acid decarboxylase using either carbidopa or benzeraside (100 μM each, 1 hour). Additionally, FEN stimulated D
            1
            R surface recruitment is blocked by the AT
            2
            R inhibitor PD123319 (1 μM, 1 hour) and the coupling defect is fully rescued by 8Br-cGMP (1 mmol/L, 1 hour), a cell permeable second messenger normally thought to signal specifically through the AT
            2
            R. We then show that FEN stimulation leads to increased production of AngIII only in the D
            1
            R/Gs coupled i22 cell line (5.82±0.43 fold, n=6, p<0.05) but not in i19 the D
            1
            R/Gs uncoupled cell line and this production was blocked with an aminopeptidase A inhibitor, EC-33 (10 μmol/L, 1 hour). Addition of 8Br-cAMP (1mmol/L 1 hour) not only leads to an increase in AngIII production, but also cGMP production (4.33±0.36 fold, n=6, p<0.05) that is blocked by PD123319 (potent, selective, non-peptide angiotensin AT
            2
            R antagonist, 1 μM, 1 hour). In summary we not only show that dopaminergic stimulation leads to increased AngIII production in a D
            1
            R coupled manner, but also that AngIII stimulation of AT
            2
            R leads to dopaminergic activation in a D
            1
            R coupled manner.
          }, booktitle={Hypertension}, author={Gildea, John J and Mallory, Micah J and Felder, Robin A}, year={2017}, month={Sep} }
 @inproceedings{mallory_gildea_xu_felder_2017, title={Abstract P326: Effects of D1R/AT2R Coupling on Aminopeptidase N (APN) in Human Renal Proximal Tubule Cells (RPTC)}, url={http://dx.doi.org/10.1161/hyp.70.suppl_1.p326}, DOI={10.1161/hyp.70.suppl_1.p326}, abstractNote={
            Dopamine receptor type 1 (D
            1
            R) and angiotensin receptor type 2 (AT
            2
            R) uncoupling from their intracellular second messengers are implicated in both salt sensitivity of blood pressure (SS) and hypertension. Angiotensin III (Ang III) and dopamine (DA) work cooperatively through binding to the interdependent D
            1
            R and AT
            2
            R to regulate renal sodium balance through autocrine signaling pathways. Aminopeptidase N (APN) is a renin-angiotensin system (RAS) enzyme localized in RPTC responsible for converting the natriuretic peptide AngIII into the anti-natriuretic agonist angiotensin IV (AngIV). The expression of APN (measured by a fluorescently labelled CD13 antibody) was investigated after increasing intracellular salt concentration with both the ionophore monensin (100 μM, 1hr.) and NaCl buffer solution (50 mmol/L, 1 hr.) in known G protein coupled (i22) and G protein uncoupled (i19) RPTC. Increasing intracellular sodium resulted in a more dramatic decrease in overall APN expression in uncoupled cells (i19 vehicle (VEH) 1.00 ± 0.03, Mon 0.87 ± 0.01 fold, n=3, p<0.05) compared to a slight decrease in coupled cells (i22 VEH 1.00 ± 0.01, NaCl 0.96 ± 0.01 fold, n=6, p<0.05). Two unknown coupling urine cell lines (RMC031-202 and RMC031-6) were evaluated alongside these known cells in an attempt to classify each as coupled or uncoupled. RMC031-202 replicated i22 (coupled) trends while RMC031-6 closely replicated i19 (uncoupled) data. Moreover, baseline APN expression comparison (normalized to i22) between the cell lines reveled a significantly elevated baseline for known and suspected uncoupled cells (i19 1.69 ± 0.047, RMC031-6 2.01 ± 0.004 fold over i22, n=3, p<0.05). Known (i22) and suspected (RMC031-202) normally coupled cells had equivalent baselines (p>0.05). An uncoupling defect may result in decreased APN regulation in RPTC causing higher baseline levels of APN expression. These increased levels of APN, in turn, lead not only to amplified production of the anti-natriuretic agonist AngIV but also reduced potential for cooperative natriuretic AngIII/DA autocrine signaling thus disrupting the dopaminergic system’s ability to suppress RAS and maintain proper sodium balance.
          }, booktitle={Hypertension}, author={Mallory, Micah J and Gildea, John J and Xu, Peng and Felder, Robin A}, year={2017}, month={Sep} }