Keith A Joiner
- Professor, Medicine
- Professor, Cellular and Molecular Medicine
- Professor, Public Health
- Professor, Economics
- Director, Scholarly Project
- Member of the Graduate Faculty
Biography for Keith A. Joiner, M.D., M.P.H. 2.21
Keith A. Joiner, M.D., M.P.H, is Professor of Medicine, Economics, Cellular and Molecular Medicine and Public Health at the University of Arizona. In 2021, he assumed the role of Director of Scholarly Projects in the University of Arizona College of Medicine, Tucson and Vice-Chair of the UA IRB.
From 2004 until 2008, he was Dean of the College of Medicine, and Vice-Provost for Medical Affairs. In 2009, he was Senior Scholar at the Association of Academic Health Centers, Washington, DC. In 2010, he moved to the Eller College of Management to create and direct the Center for Management Innovations in Healthcare, and to teach and conduct research in health economics.
Before moving to the University of Arizona, he was Chief of the Section of Infectious Diseases and the Waldemar von Zedtwitz Professor of Medicine, Cell Biology and Epidemiology at the Yale University School of Medicine. Prior to that he was Head of the Unit of Microbial Pathogenesis at the National Institutes of Health, Bethesda, MD.
He was in the top 5% of all NIH grant recipients in the period from 1980-2005. At Yale University, he created and directed the Investigative Medicine Program, a PhD program for MDs with at least two years of residency experience, that formed the basis for the Yale Clinical and Translational Science Award.
He has published more than 260 manuscripts and chapters. His research spans the gamut from the basic immunobiology and cell biology of infectious diseases, to optimizing resource allocation in academic health centers, to healthcare payment and delivery reform. Currently, his research focuses on novel health insurance design, physician decision making, and the relationship of electronic health records to charge capture – the process of generating claims (bills) for submission to insurers.
- Yale University, New Haven, Connecticut, United States
- M.D. Medicine
- University of Colorado, Denver, Colorado, United States
- University of Chicago, Chicago, Illinois, United States
- various (1974 - Ongoing)
Health Economics and Policy
Health Economics and Policy;Behavioral Economics;Health Insurance Design;Physician Decision Making;Electronic Medical Records and Health Care Payment
Health EconomicsECON 556 (Fall 2023)
Health EconomicsECON 556 (Spring 2023)
Scholarly ProjectMED 820B (Spring 2023)
Scholarly ProjectMED 820D (Spring 2023)
Health EconomicsECON 556 (Fall 2022)
Independent StudyHPS 699 (Fall 2022)
Scholarly ProjectMED 820A (Fall 2022)
Scholarly ProjectMED 820C (Fall 2022)
Health EconomicsECON 556 (Spring 2022)
Scholarly ProjectMED 820B (Spring 2022)
Health EconomicsECON 556 (Fall 2021)
Scholarly ProjectMED 820A (Fall 2021)
Health EconomicsECON 556 (Spring 2021)
Honors ThesisECON 498H (Spring 2021)
Honors ThesisHPS 498H (Spring 2021)
Crnt Tps: Hlthcare Econ\PolicyECON 427 (Fall 2020)
Crnt Tps: Hlthcare Econ\PolicyECON 527 (Fall 2020)
Health EconomicsECON 556 (Fall 2020)
Honors ThesisECON 498H (Fall 2020)
Honors ThesisHPS 498H (Fall 2020)
Crnt Tps: Hlthcare Econ\PolicyECON 427 (Spring 2020)
Crnt Tps: Hlthcare Econ\PolicyECON 527 (Spring 2020)
Health EconomicsECON 556 (Spring 2020)
Crnt Tps: Hlthcare Econ\PolicyECON 427 (Fall 2019)
Crnt Tps: Hlthcare Econ\PolicyECON 527 (Fall 2019)
Health EconomicsECON 556 (Fall 2019)
Crnt Tps: Hlthcare Econ\PolicyECON 427 (Spring 2019)
Crnt Tps: Hlthcare Econ\PolicyECON 527 (Spring 2019)
Health EconomicsECON 556 (Spring 2019)
Honors ThesisECON 498H (Spring 2019)
Crnt Tps: Hlthcare Econ\PolicyECON 427 (Fall 2018)
Health EconomicsECON 556 (Fall 2018)
Honors ThesisECON 498H (Fall 2018)
Crnt Tps: Hlthcare Econ\PolicyECON 427 (Spring 2018)
Crnt Tps: Hlthcare Econ\PolicyECON 527 (Spring 2018)
Health EconomicsECON 556 (Spring 2018)
Honors ThesisECON 498H (Spring 2018)
Crnt Tps: Hlthcare Econ\PolicyECON 427 (Fall 2017)
Honors ThesisECON 498H (Fall 2017)
Crnt Tps: Hlthcare Econ\PolicyECON 427 (Spring 2017)
Crnt Tps: Hlthcare Econ\PolicyECON 527 (Spring 2017)
Health EconomicsECON 556 (Spring 2017)
Crnt Tps: Hlthcare Econ\PolicyECON 427 (Fall 2016)
Crnt Tps: Hlthcare Econ\PolicyECON 527 (Fall 2016)
Health EconomicsECON 556 (Fall 2016)
Honors ThesisECON 498H (Fall 2016)
Crnt Tps: Hlthcare Econ\PolicyECON 427 (Spring 2016)
Crnt Tps: Hlthcare Econ\PolicyECON 527 (Spring 2016)
Honors ThesisECON 498H (Spring 2016)
- Coleman, D. L., & Joiner, K. A. (2021). Physician Incentive Compensation Plans in Academic Medical Centers: The Imperative to Prioritize Value. The American journal of medicine, 134(11), 1344-1349.More infoThe emphasis on clinical volume in physician compensation plans has diminished professional vitality in academic medical centers and increased the cost of health care. Physician incentive compensation plans that focus on clinical volume can distort clinical encounters and fail to incorporate the professionalism and intrinsic motivators of clinicians. We assert herein that physician incentive compensation plans should reward clinical value (quality/cost) rather than clinical volume. The recommended change is compelled by the tenets of medical professionalism, the need to cultivate meaning in clinical practice, and the urgent financial and moral imperatives to improve health outcomes and reduce cost. The design of physician incentive compensation plans should incorporate accurate and valid measures of quality and cost, behavioral economic considerations, transparency and equity, prospective assessment of the impact on key outcomes, and flexible elements that encourage innovation and preserve fidelity to unique practice circumstances. Physicians should be recognized in compensation plans for enhancing the value of care, inspiring and educating the future clinical workforce, and improving public health through discovery.
- Robertson, C. T., Schaefer, K. A., Scheitrum, D., Puig, S., & Joiner, K. (2021). Indemnifying precaution: economic insights for regulation of a highly infectious disease. Journal of law and the biosciences, 7(1), lsaa032.More infoEconomic insights are powerful for understanding the challenge of managing a highly infectious disease, such as COVID-19, through behavioral precautions including social distancing. One problem is a form of moral hazard, which arises when some individuals face less personal risk of harm or bear greater personal costs of taking precautions. Without legal intervention, some individuals will see socially risky behaviors as personally less costly than socially beneficial behaviors, a balance that makes those beneficial behaviors unsustainable. For insights, we review health insurance moral hazard, agricultural infectious disease policy, and deterrence theory, but find that classic enforcement strategies of punishing noncompliant people are stymied. One mechanism is for policymakers to indemnify individuals for losses associated with taking those socially desirable behaviors to reduce the spread. We develop a coherent approach for doing so, based on conditional cash payments and precommitments by citizens, which may also be reinforced by social norms.
- Joiner, K. A. (2020). Airplanes spread diseases rapidly - so maybe unvaccinated people shouldn't be allowed to fly. The Conversation.
- Joiner, K. A. (2020). Distinguishing moral hazard from access for high cost healthcare under insurance. PlosOne, 15(4), 1-14.
- Joiner, K. A. (2020). In the rush to innovate for COVID-19 drugs, sound science is essential. The Conversation.
- Joiner, K. A. (2020). Indemnifying precaution: Economics insights for regulation of a highly-infectious disease. Journal of the Law and Biosciences, 7(1), 1-14.
- Robertson, C. T., Yuan, A., Zhang, W., & Joiner, K. (2020). Distinguishing moral hazard from access for high-cost healthcare under insurance. PloS one, 15(4), e0231768.More infoHealth policy has long been preoccupied with the problem that health insurance stimulates spending ("moral hazard"). However, much health spending is costly healthcare that uninsured individuals could not otherwise access. Field studies comparing those with more or less insurance cannot disaggregate moral hazard versus access. Moreover, studies of patients consuming routine low-dollar healthcare are not informative for the high-dollar healthcare that drives most of aggregate healthcare spending in the United States.
- Al Mohajer, M., Joiner, K. A., & Nix, D. E. (2018). Are Teaching Hospitals Treated Fairly in the Hospital-Acquired Condition Reduction Program?. Academic medicine : journal of the Association of American Medical Colleges, 93(12), 1827-1832.More infoTo identify the factors associated with total Hospital-Acquired Condition Reduction Program (HACRP) score and with receiving a Centers for Medicare and Medicaid Services (CMS) penalty (1% reduction in payment to those hospitals in the lowest-performing quartile of HACRP scores) for fiscal years (FYs) 2015-2017 with a particular focus on trends over this period.
- Johnstone, C., Joiner, K. A., Pierce, J., & Krouse, R. S. (2018). Mohs Micrographic Surgery Volume and Payment Patterns Among Dermatologists in the Medicare Population, 2013. American journal of clinical oncology, 41(12), 1199-1203.More infoMohs micrographic surgery (MMS) has expanded markedly in recent years but there is limited information on volume, practice patterns or reimbursement. This study characterizes MMS utilization in the Medicare population.
- Joiner, K. A., & Joiner, K. A. (2017). Maternity Coverage and the American Health Care Act: A Tragedy in Two Acts (So Far).. American Journal of Clinical and Experimental Obstetrics and Gynecology, 4, 44-47.
- Seckeler, M. D., Thomas, I. D., Andrews, J., Joiner, K., & Klewer, S. E. (2016). A review of the economics of adult congenital heart disease. Expert review of pharmacoeconomics & outcomes research, 16(1), 85-96.More infoAdults living with congenital heart disease (CHD) now outnumber children with the disease. Thanks to medical advances over the past 75 years, many of these fatal childhood heart problems have changed to chronic medical conditions. As the population of adults with CHD increases, they will require increasingly complex medical, surgical and catheter-based therapies. In addition, social burdens including education, employment and insurability, which increase the societal costs of adult CHD, are now being recognized for adults living with CHD. This review summarizes the available literature on the economics of adult CHD.
- Malanga, S., Sprissler, R., Robertson, C., & Joiner, K. (2015). A problem not yet manifest: gaps in insurance coverage of medical interventions after genetic testing. Journal of law and the biosciences, 2(3), 729-735.
- Joiner, K. A., & Coleman, D. L. (2012). Perspective: key indicators in academic medicine: a suggested framework for analysis. Academic medicine : journal of the Association of American Medical Colleges, 87(2), 230-5.More infoKey Indicators in Academic Medicine (KIAMs), a new feature in Academic Medicine, are intended to substantially inform teaching hospitals and medical schools on those metrics that may best gauge their health, including the performance of units and programs within these organizations. Ultimately, KIAMs may promote effective growth and development in a dynamic clinical, training, and research environment. At the outset of this laudable feature, the authors of this perspective offer a suggested framework for analyzing key indicators with the goal of enhancing the usefulness of the published KIAMs. They outline their view of pitfalls and opportunities in the development of key indicators and suggest strategies. The authors close by suggesting how this feature could form the framework for a comprehensive national project.
- Lige, B., Romano, J. D., Sampels, V., Sonda, S., Joiner, K. A., & Coppens, I. (2012). Introduction of caveolae structural proteins into the protozoan Toxoplasma results in the formation of heterologous caveolae but not caveolar endocytosis. PloS one, 7(12), e51773.More infoPresent on the plasma membrane of most metazoans, caveolae are specialized microdomains implicated in several endocytic and trafficking mechanisms. Caveolins and the more recently discovered cavins are the major protein components of caveolae. Previous studies reported that caveolar invaginations can be induced de novo on the surface of caveolae-negative mammalian cells upon heterologous expression of caveolin-1. However, it remains undocumented whether other components in the transfected cells participate in caveolae formation. To address this issue, we have exploited the protozoan Toxoplasma as a heterologous expression system to provide insights into the minimal requirements for caveogenesis and caveolar endocytosis. Upon expression of caveolin-1, Toxoplasma accumulates prototypical exocytic caveolae 'precursors' in the cytoplasm. Toxoplasma expressing caveolin-1 alone, or in conjunction with cavin-1, neither develops surface-located caveolae nor internalizes caveolar ligands. These data suggest that the formation of functional caveolae at the plasma membrane in Toxoplasma and, by inference in all non-mammalian cells, requires effectors other than caveolin-1 and cavin-1. Interestingly, Toxoplasma co-expressing caveolin-1 and cavin-1 displays an impressive spiraled network of membranes containing the two proteins, in the cytoplasm. This suggests a synergistic activity of caveolin-1 and cavin-1 in the morphogenesis and remodeling of membranes, as illustrated for Toxoplasma.
- Joiner, K. A., Castellanos, N., & Wartman, S. A. (2011). Resource allocation in academic health centers: creating common metrics. Academic medicine : journal of the Association of American Medical Colleges, 86(9), 1084-92.More infoOptimizing resource allocation is essential for effective academic health center (AHC) management, yet guidelines and principles for doing so in the research and educational arenas remain limited. To address this issue, the authors analyzed responses to the 2007-2008 Association of Academic Health Centers census using ratio analysis. The concept was to normalize data from an individual institution to that same institution, by creating a ratio of two separate values from the institution (e.g., total faculty FTEs/total FTEs). The ratios were then compared across institutions. Generally, this strategy minimizes the effect of institution size on the responses, size being the predominant limitation of using absolute values for developing meaningful metrics. In so doing, ratio analysis provides a range of responses that can be displayed in graphical form to determine the range and distribution of values. The data can then be readily scrutinized to determine where any given institution falls within the distribution. Staffing ratios and operating ratios from up to 54 institutions are reported. For ratios including faculty numbers in the numerator or denominator, the range of values is wide and minimally discriminatory, reflecting heterogeneity across institutions in faculty definitions. Values for financial ratios, in particular total payroll expense/total operating expense, are more tightly clustered, reflecting in part the use of units with a uniform definition (i.e., dollars), and emphasizing the utility of such ratios in decision guidelines. The authors describe how to apply these insights to develop metrics for resource allocation in the research and educational arenas.
- Ehrenman, K., Sehgal, A., Lige, B., Stedman, T. T., Joiner, K. A., & Coppens, I. (2010). Novel roles for ATP-binding cassette G transporters in lipid redistribution in Toxoplasma. Molecular microbiology, 76(5), 1232-49.More infoToxoplasma is a protozoan parasite proficiently adapted to thrive in a parasitophorous vacuole (PV) formed in the cytoplasm of a large variety of mammalian cells. As an actively dividing organism, the parasite must adjust the lipid composition of its membranes to preserve organelle vitality and expand the size of the PV membrane to accommodate growing progeny. We showed that Toxoplasma takes up host lipids and can expel major lipids in an ATP-dependent process. In order to provide detailed mechanistic insights into lipid trafficking phenomena relevant to Toxoplasma biology, we characterized six parasite ATP-binding cassette (ABC) G family transporters and investigated their potential contribution to lipid homeostatic processes. All these transporters are expressed in the parasite and five of them are upregulated upon exposure to sterols. Four ABCG are localized to secretory organelles and the plasma membrane, and promote cholesterol and phospholipid efflux, reflecting the importance in exportation of large amounts of lipids into the PV. Interestingly, one ABCG that is associated with vesicles in the PV and the plasma membrane acts as a cholesterol importer. This last finding expands our current view on the role of some ABCG transporters in eukaryotic sterol influx.
- Joiner, K., & Joiner, K. A. (2009). A simple model to optimize resource allocations when expanding the faculty research base: a case study. Academic medicine : journal of the Association of American Medical Colleges, 84(1).More infoConstruction of new biomedical research facilities has outpaced the funding sources for faculty to occupy those facilities. This puts a premium on the efficient allocation of central resources for faculty recruitment. The author developed a mathematical model to determine the optimal structure (dollars, space) for allocating resource packages when recruiting new faculty, based on expected financial returns from those faculty. Surprisingly, the optimal strategy was to allocate homogeneous recruitment packages, independent of the recruited faculty member's rank or the individual's expected revenue generation. Optimization results were used to allocate recruitment packages to new department head and center directors in the University of Arizona College of Medicine during the last four years (2005-2008). At any institution that uses this model, appropriate distribution of facilities and administrative revenues at the institution is needed to equitably balance the costs and benefits associated with faculty expansion.
- Joiner, K., & Joiner, K. A. (2009). Commentary: Evaluating faculty productivity in research: an interesting approach, but questions remain. Academic medicine : journal of the Association of American Medical Colleges, 84(11).More infoAcademic institutions must have strategies for evaluating research productivity by faculty. Such strategies are useful in guiding resource allocations for the research enterprise, for decisions on faculty promotions, and for broader institutional planning, including program development. Commonly, decisions about research space utilization, and funding to support the space, are considered within the purview of the institutional administration. Peer review, in manuscript and grant submissions and the promotions process, is more commonly used to evaluate the impact of faculty research. The article by Iyengar et al in this issue of Academic Medicine takes an interesting approach to evaluate research productivity of individual faculty by integrating benchmarks for research funding and publication impact. The strategy of using these benchmarks to partition faculty into quadrants to guide faculty development activities is clever and useful. Less clear are the philosophy and long-term utility of the approach. The applicability to the stated goal of promoting multidisciplinary and interdisciplinary translational research is not obvious, nor is it apparent that faculty will continue to view decisions as transparent and fair over the longer term. Nevertheless, the authors' article is a welcome contribution at a time when many institutions are struggling with issues of evaluating faculty investigators and allocating resources for research.
- Joiner, K. A., Libecap, A., Cress, A. E., Wormsley, S., St Germain, P., Berg, R., & Malan, P. (2008). Supporting the academic mission in an era of constrained resources: approaches at the University of Arizona College of Medicine. Academic medicine : journal of the Association of American Medical Colleges, 83(9), 837-44.More infoThe authors describe initiatives at the University of Arizona College of Medicine to markedly expand faculty, build research along programmatic lines, and promote a new, highly integrated medical school curriculum. Accomplishing these goals in this era of declining resources is challenging. The authors describe their approaches and outcomes to date, derived from a solid theoretical framework in the management literature, to (1) support research faculty recruitment, emphasizing return on investment, by using net present value to guide formulation of recruitment packages, (2) stimulate efficiency and growth through incentive plans, by using utility theory to optimize incentive plan design, (3) distribute resources to support programmatic growth, by allocating research space and recruitment dollars to maximize joint hires between units with shared interests, and (4) distribute resources from central administration to encourage medical student teaching, by aligning state dollars to support a new integrated organ-system based-curriculum. Detailed measurement is followed by application of management principles, including mathematical modeling, to make projections based on the data collected. Although each of the initiatives was developed separately, they are linked functionally and financially, and they are predicated on explicitly identifying opportunity costs for all major decisions, to achieve efficiencies while supporting growth. The overall intent is to align institutional goals in education, research, and clinical care with incentives for unit heads and individual faculty to achieve those goals, and to create a clear line of sight between expectations and rewards. Implementation is occurring in a hypothesis-driven fashion, permitting testing and refinement of the strategies.
- Joiner, K., Elliott, D. A., McIntosh, M. T., Hosgood, H. D., Chen, S., Zhang, G., Baevova, P., & Joiner, K. A. (2008). Four distinct pathways of hemoglobin uptake in the malaria parasite Plasmodium falciparum. Proceedings of the National Academy of Sciences of the United States of America, 105(7).More infoDuring the bloodstage of malaria infection, the parasite internalizes and degrades massive amounts of hemoglobin from the host red blood cell. Using serial thin-section electron microscopy and three-dimensional reconstruction, we demonstrate four independent, but partially overlapping, hemoglobin-uptake processes distinguishable temporally, morphologically, and pharmacologically. Early ring-stage parasites undergo a profound morphological transformation in which they fold, like a cup, onto themselves and in so doing take a large first gulp of host cell cytoplasm. This event, which we term the "Big Gulp," appears to be independent of actin polymerization and marks the first step in biogenesis of the parasite's lysosomal compartment-the food vacuole. A second, previously identified uptake process, uses the cytostome, a well characterized and morphologically distinct structure at the surface of the parasite. This process is more akin to classical endocytosis, giving rise to small (
- Joiner, K., Libecap, A., Wormsley, S., Cress, A., Matthews, M., Souza, A., & Joiner, K. A. (2008). A comprehensive space management model for facilitating programmatic research. Academic medicine : journal of the Association of American Medical Colleges, 83(3).More infoIn FY04, the authors developed and implemented models to manage existing and incremental research space, and to facilitate programmatic research, at the University of Arizona College of Medicine. Benchmarks were set for recovery of total sponsored research dollars and for facilities and administrative (F&A) dollars/net square foot (nsf) of space, based on college-wide metrics. Benchmarks were applied to units (departments, centers), rather than to individual faculty. Performance relative to the benchmark was assessed using three-year moving averages, and applied to existing blocks of space. Space was recaptured or allocated, in all cases to programmatic themes, using uniform policies. F&A revenues were returned on the basis of performance relative to a benchmark. During the first two years after implementation of the model (FY05 and FY06), and for the 24 units occupying research space, median total sponsored research revenue/nsf increased from $393.96 to $474.46 (20.4%), and median F&A revenue/nsf increased from $57.42 to $91.86 (60.0%). These large increases in median values are driven primarily from redistribution and recapturing of space. Recruiting policies for unit heads were developed to facilitate joint hires among units. In combination, these policies created a comprehensive space management model for facilitating programmatic research. Although challenges remain in implementing the programmatic recruitment strategy, and selected modifications to the original policy were introduced later (e.g., research space for newly recruited junior faculty is now exempted from calculations for three years), overall, the models have created a climate of transparency that is now accepted and that allows efficient and equitable management of research space.
- Roberts, L., Egan, T. J., Joiner, K. A., & Hoppe, H. C. (2008). Differential effects of quinoline antimalarials on endocytosis in Plasmodium falciparum. Antimicrobial agents and chemotherapy, 52(5), 1840-2.More infoThe effects of quinoline antimalarials on endocytosis by Plasmodium falciparum was investigated by measuring parasite hemoglobin levels, peroxidase uptake, and transport vesicle content. Mefloquine, quinine, and halofantrine inhibited endocytosis, and chloroquine inhibited vesicle trafficking, while amodiaquine shared both effects. Protease inhibitors moderated hemoglobin perturbations, suggesting a common role for heme binding.
- Smythe, W. A., Joiner, K. A., & Hoppe, H. C. (2008). Actin is required for endocytic trafficking in the malaria parasite Plasmodium falciparum. Cellular microbiology, 10(2), 452-64.More infoThe intra-erythrocytic stages of the malaria parasite endocytose large quantities of the surrounding erythrocyte cytoplasm and deliver it to a digestive food vacuole via endocytic vesicles. Digestion provides amino acids for parasite protein synthesis and is required to maintain the osmotic integrity of the host cell. The parasite endocytic pathway has been described morphologically by electron microscopy, but the molecular mechanisms that mediate and regulate it remain elusive. Given the involvement of actin in endocytosis in other eukaryotes, we have used actin inhibitors to assess the requirement for this protein in the endocytic pathway of the human malaria parasite, Plasmodium falciparum. Treatment of cultures with cytochalasin D did not affect haemoglobin levels in the parasites when co-administered with protease inhibitors, and neither did it affect the uptake of the endocytic tracer horseradish peroxidase, suggesting the absence of actin in the mechanism of endocytosis. However, in the absence of protease inhibitors, treated parasites contained increased levels of haemoglobin due to an accumulation of enlarged endocytic vesicles, as determined by immunofluorescence and electron microscopy, suggesting a role for actin in vesicle trafficking, possibly by mediating vesicle maturation and/or fusion to the digestive vacuole. In contrast to cytochalasin D, treatment with jasplakinolide led to an inhibition of endocytosis, an accumulation of vesicles closer to the plasma membrane and a marked concentration of actin in the parasite cortex. We propose that the stabilization of cortical actin filaments by jasplakinolide interferes with normal endocytic vesicle formation and migration from the cell periphery.
- Joiner, K. A., Hiteman, S., Wormsley, S., & St Germain, P. (2007). Timing of revenue streams from newly recruited faculty: implications for faculty retention. Academic medicine : journal of the Association of American Medical Colleges, 82(12), 1228-38.More infoTo determine the timing and magnitude of revenues generated by newly recruited faculty, to facilitate configuration of recruitment packages appropriately matched to expected financial returns.
- Joiner, K. A., Schloss, E. P., Philip Malan, T., Flynn, S. D., & Chadwick, J. A. (2007). Phoenix rises, with Tucson's help: establishing the first four-year allopathic program in the nation's fifth largest city. Academic medicine : journal of the Association of American Medical Colleges, 82(12), 1126-38.More infoThe authors describe the expansion of The University of Arizona College of Medicine from Tucson, Arizona, into Phoenix. They explain how the new Phoenix program, in partnership with Arizona State University, is one college of medicine for the state of Arizona, governed by a single accreditation by the Liaison Committee for Medical Education (LCME). The authors present 21 lessons to be considered early in a medical school expansion process: clearly establish responsibility, authority, and accountability; define activities under university purview and those that require broader engagement; delineate college-wide versus campus-specific functions; clearly define the intent of the new initiative; get frequent input from the LCME; use LCME input to ensure a student focus; be cautious in using consultants; use respected local "brokers"; create a single locus for input and concerns; educate constituencies about medical school requirements; engage leadership to create linkages across sites; encourage communication between leaders in both sites; discriminate between shared and distinctive local curriculum elements; consider the effort and experience required to develop a full curriculum versus those required to develop specific local curricular areas; create simple, transparent admission processes; define faculty profiles for the new program; ensure sufficient resources for core faculty; budget based on national metrics; create core mission-based principles to frame discussions and decisions; segregate clinical affiliation discussions from curriculum and recruitment of basic science faculty; and ensure sufficient land. Although these observations are most relevant to institutions planning expansions of already accredited programs, they derive from principles and practical considerations with wider applicability.
- McIntosh, M. T., Vaid, A., Hosgood, H. D., Vijay, J., Bhattacharya, A., Sahani, M. H., Baevova, P., Joiner, K. A., & Sharma, P. (2007). Traffic to the malaria parasite food vacuole: a novel pathway involving a phosphatidylinositol 3-phosphate-binding protein. The Journal of biological chemistry, 282(15), 11499-508.More infoPhosphatidylinositol 3-phosphate (PI3P) is a key ligand for recruitment of endosomal regulatory proteins in higher eukaryotes. Subsets of these endosomal proteins possess a highly selective PI3P binding zinc finger motif belonging to the FYVE domain family. We have identified a single FYVE domain-containing protein in Plasmodium falciparum which we term FCP. Expression and mutagenesis studies demonstrate that key residues are involved in specific binding to PI3P. In contrast to FYVE proteins in other organisms, endogenous FCP localizes to a lysosomal compartment, the malaria parasite food vacuole (FV), rather than to cytoplasmic endocytic organelles. Transfections of deletion mutants further indicate that FCP is essential for trophozoite and FV maturation and that it traffics to the FV via a novel constitutive cytoplasmic to vacuole targeting pathway. This newly discovered pathway excludes the secretory pathway and is directed by a C-terminal 44-amino acid peptide domain. We conclude that an FYVE protein that might be expected to participate in vesicle targeting in the parasite cytosol instead has a vital and functional role in the malaria parasite FV.
- Shea, M., Jäkle, U., Liu, Q., Berry, C., Joiner, K. A., & Soldati-Favre, D. (2007). A family of aspartic proteases and a novel, dynamic and cell-cycle-dependent protease localization in the secretory pathway of Toxoplasma gondii. Traffic (Copenhagen, Denmark), 8(8), 1018-34.More infoAspartic proteases are important virulence factors in pathogens like HIV, Candida albicans or Plasmodium falciparum. We report here the identification of seven putative aspartic proteases, TgASP1 to TgASP7, in the apicomplexan parasite Toxoplasma gondii. Bioinformatic and phylogenetic analysis of the TgASPs and other aspartic proteases from related Apicomplexa suggests the existence of five distinct groups of aspartic proteases with different evolutionary lineages. The members of each group share predicted biological features that validate the phylogeny. TgASP1 is expressed in tachyzoites, the rapidly dividing asexual stage of T.gondii. We present the proteolytic maturation and subcellular localization of this protease through the cell cycle. TgASP1 shows a novel punctate localization associated with the secretory system in non-dividing cells, and relocalizes dramatically and unambiguously to the nascent inner membrane complex of daughter cells at replication, before coalescing again at the end of division.
- Coppens, I., Dunn, J. D., Romano, J. D., Pypaert, M., Zhang, H., Boothroyd, J. C., & Joiner, K. A. (2006). Toxoplasma gondii sequesters lysosomes from mammalian hosts in the vacuolar space. Cell, 125(2), 261-74.More infoThe intracellular compartment harboring Toxoplasma gondii satisfies the parasite's nutritional needs for rapid growth in mammalian cells. We demonstrate that the parasitophorous vacuole (PV) of T. gondii accumulates material coming from the host mammalian cell via the exploitation of the host endo-lysosomal system. The parasite actively recruits host microtubules, resulting in selective attraction of endo-lysosomes to the PV. Microtubule-based invaginations of the PV membrane serve as conduits for the delivery of host endo-lysosomes within the PV. These tubular conduits are decorated by a parasite coat, including the tubulogenic protein GRA7, which acts like a garrote that sequesters host endocytic organelles in the vacuolar space. These data define an unanticipated process allowing the parasite intimate and concentrated access to a diverse range of low molecular weight components produced by the endo-lysosomal system. More generally, they identify a unique mechanism for unidirectional transport and sequestration of host organelles.
- Massimine, K. M., McIntosh, M. T., Doan, L. T., Atreya, C. E., Gromer, S., Sirawaraporn, W., Elliott, D. A., Joiner, K. A., Schirmer, R. H., & Anderson, K. S. (2006). Eosin B as a novel antimalarial agent for drug-resistant Plasmodium falciparum. Antimicrobial agents and chemotherapy, 50(9), 3132-41.More info4',5'-Dibromo-2',7'-dinitrofluorescein, a red dye commonly referred to as eosin B, inhibits Toxoplasma gondii in both enzymatic and cell culture studies with a 50% inhibitory concentration (IC(50)) of 180 microM. As a non-active-site inhibitor of the bifunctional T. gondii dihydrofolate reductase-thymidylate synthase (DHFR-TS), eosin B offers a novel mechanism for inhibition of the parasitic folate biosynthesis pathway. In the present study, eosin B was further evaluated as a potential antiparasitic compound through in vitro and cell culture testing of its effects on Plasmodium falciparum. Our data revealed that eosin B is a highly selective, potent inhibitor of a variety of drug-resistant malarial strains, with an average IC(50) of 124 nM. Furthermore, there is no indication of cross-resistance with other clinically utilized compounds, suggesting that eosin B is acting via a novel mechanism. The antimalarial mode of action appears to be multifaceted and includes extensive damage to membranes, the alteration of intracellular organelles, and enzymatic inhibition not only of DHFR-TS but also of glutathione reductase and thioredoxin reductase. In addition, preliminary studies suggest that eosin B is also acting as a redox cycling compound. Overall, our data suggest that eosin B is an effective lead compound for the development of new, more effective antimalarial drugs.
- Wilson, M. S., Joiner, K. A., Inzucchi, S. E., Mulligan, G. J., Mechem, M. F., Gross, C. P., & Coleman, D. L. (2006). Improving clinical productivity in the academic setting: a novel incentive plan based on utility theory. Academic medicine : journal of the Association of American Medical Colleges, 81(4), 306-13.More infoAcademic internal medicine practices face growing challenges to financial viability due to high overhead, competing institutional missions, and suboptimal physician productivity. The authors describe the development of a clinical incentive plan for a group of academic subspecialty physicians at the Dana Clinic, an outpatient setting at Yale School of Medicine, and report on results of the first year's experience under the plan.
- Joiner, K., & Joiner, K. A. (2005). Avoiding the winner's curse in faculty recruitment. The American journal of medicine, 118(11).
- Joiner, K., & Joiner, K. A. (2005). The not-for-profit form and translational research: Kerr revisited?. Journal of translational medicine, 3(1).More infoTranslational research conducted in academic health centers is confounded by the organizational structure in which the work is performed. Investigators must obtain research funding and appropriate recognition as a part of a research team in a not-for-profit environment which has more readily rewarded basic work, and individual accomplishments. What results is a unique form of conflict of interest, best understood by relating the basic principles underlying the not-for-profit form to the conduct of translational research in the AHC setting.
- Massimine, K. M., Doan, L. T., Atreya, C. A., Stedman, T. T., Anderson, K. S., Joiner, K. A., & Coppens, I. (2005). Toxoplasma gondii is capable of exogenous folate transport. A likely expansion of the BT1 family of transmembrane proteins. Molecular and biochemical parasitology, 144(1), 44-54.More infoFolates are key elements in eukaryotic biosynthetic processes. The protozoan parasite Toxoplasma gondii possesses the enzymes necessary for de novo folate synthesis and has been suggested to lack alternative mechanisms for folate acquisition. In this paper, we present a different view by providing evidence that Toxoplasma is capable of salvaging exogenous folates. By monitoring uptake of radiolabeled folates by parasites in axenic conditions, our studies revealed a common folate transporter that has a high affinity for folic acid. Transport of this compound across the parasite plasma membrane is rapid, biphasic, temperature dependent, bi-directional, concentration dependent and specific. In addition, morphological evidence demonstrates that fluorescent methotrexate, a folate analog, is internalized by Toxoplasma and shows localization reminiscent to the mitochondrion. The presence of putative folate transporter genes in the Toxoplasma genome, which are homologous to the BT1 family of proteins, suggests that Toxoplasma may encode proteins involved in folate transport. Interestingly, genome analysis suggests that the BT1 family of proteins exists not only in Toxoplasma, but in other Apicomplexan parasites as well. Altogether, our results not only have implications for current therapeutic regimens against T. gondii, but they also allude that the folate transport mechanism may represent a novel Apicomplexan target for the development of new drugs.
- Sehgal, A., Bettiol, S., Pypaert, M., Wenk, M. R., Kaasch, A., Blader, I. J., Joiner, K. A., & Coppens, I. (2005). Peculiarities of host cholesterol transport to the unique intracellular vacuole containing Toxoplasma. Traffic (Copenhagen, Denmark), 6(12), 1125-41.More infoThe intracellular protozoan Toxoplasma gondii is auxotrophic for low-density lipoprotein (LDL)-derived cholesterol (C). We previously showed that T. gondii scavenges this essential lipid from host endolysosomal compartments and that C delivery to the parasitophorous vacuole (PV) does not require transit through host Golgi or endoplasmic reticulum. In this study, we explore the itinerary of C from the host endolysosomes to the PV. Labeled C incorporated into LDL is rapidly detected in intravacuolar parasites and partially esterified by the parasites. In contrast to diverse mammalian organelles, the post-endolysosomal transfer of C to the PV does not involve the host plasma membrane as an intermediate. Nevertheless, the PV membrane is accessible to extracellular sterol acceptors, suggesting C trafficking from intracellular parasites to host plasma membrane. C movement to the PV requires temperatures permissive for vesicular transport, metabolic energy and functional microtubules. Host caveolae vesicles and the sterol carrier protein-2 do not participate in this process. Proteolytic treatment of purified PV or free parasites abolishes C acquisition by the parasites. Altogether, these results support a vesicular transport system from host endolysosomes to the PV, and a requirement for PV membrane and parasite plasma membrane proteins in C delivery to T. gondii.