Craig C Weinkauf
- Assistant Professor, Surgery
I was born in Tucson, Arizona but mostly raised in Washoe Valley, Nevada. I completed my BA in Biology at the University of San Diego; I completed my MD/PhD (Immunology) at Tufts University in Boston, MA; I completed my training in Vascular Surgery at the University of Arizona.
I am an Assisstant Professor of Surgery at the University of Arizona. My clinical practice is to take care of patients with vascular disease. This includes the broad spectrum of patients with arterial, venous or lymphatic pathologies.
My research focuses on understanding how extracranial carotid atherosclerosis affects brain structure and cognition. I use my background as an Immunologist for this purpose as well as strong collaborations with faculty from the department of medical imaging, psychiatry, neurology and psychology.
- M.D. Medicine
- Tufts University, Boston, Massachusetts, United States
- Ph.D. Immunology
- Tufts University, Boston, Massachusetts, United States
- Inflammation and associated Cell Death of the Enteric Nervous System associated with Trypanosoma crzui infection.
- Banner University Medical Center - Tucson (2017 - Ongoing)
- Career Development Award
- University of Arizona Health Sciences, Spring 2019
Licensure & Certification
- Registered Physciain in Vascular Interpretation (RPVI), Alliance For Physician Certification & Advancement (2016)
No activities entered.
ThesisCMM 910 (Spring 2021)
ThesisCMM 910 (Fall 2020)
- Weinkauf, C. C. (2017). Difficult Decisions in Vascular Surgery. In Decisions in Surgery: An Evidence-Based Approach.. Switzerland: Springer International.
- Weinkauf, C. C. (2015). Technological Advances in Endovascular Surgery. In Technological Advances in Surgery, Trauma & Critical Care. New York, New York: Springer.
- Pandit, V., Zeeshan, M., Nelson, P. R., Hamidi, M., Jhajj, S., Lee, A., Trinidad, B., Goshima, K., Horst, V., Weinkauf, C., Zhou, W., & Tan, T. W. (2020). Frailty Syndrome in Patients with Carotid Disease: Simplifying How We Calculate Frailty. Annals of vascular surgery, 62, 159-165.More infoFrailty syndrome is an established predictor of adverse outcomes after carotid surgery. Recently, a modified 5-factor National Surgical Quality Improvement Program frailty index has been used; however, its utility in vascular procedures is unclear. The aim of our study was to compare the 5-factor modified frailty index (mFI-5) with the 11-factor modified frailty index (mFI-11) regarding value and predictive ability for mortality, postoperative infection, and unplanned 30-day readmission.
- Ripperger, T. J., Uhrlaub, J. L., Watanabe, M., Wong, R., Castaneda, Y., Pizzato, H. A., Thompson, M. R., Bradshaw, C., Weinkauf, C. C., Bime, C., Erickson, H. L., Knox, K., Bixby, B., Parthasarathy, S., Chaudhary, S., Natt, B., Cristan, E., Aini, T. E., Rischard, F., , Campion, J., et al. (2020). Detection, prevalence, and duration of humoral responses to SARS-CoV-2 under conditions of limited population exposure. medRxiv : the preprint server for health sciences.More infoWe conducted an extensive serological study to quantify population-level exposure and define correlates of immunity against SARS-CoV-2. We found that relative to mild COVID-19 cases, individuals with severe disease exhibited elevated authentic virus-neutralizing titers and antibody levels against nucleocapsid (N) and the receptor binding domain (RBD) and the S2 region of spike protein. Unlike disease severity, age and sex played lesser roles in serological responses. All cases, including asymptomatic individuals, seroconverted by 2 weeks post-PCR confirmation. RBD- and S2-specific and neutralizing antibody titers remained elevated and stable for at least 2-3 months post-onset, whereas those against N were more variable with rapid declines in many samples. Testing of 5882 self-recruited members of the local community demonstrated that 1.24% of individuals showed antibody reactivity to RBD. However, 18% (13/73) of these putative seropositive samples failed to neutralize authentic SARS-CoV-2 virus. Each of the neutralizing, but only 1 of the non-neutralizing samples, also displayed potent reactivity to S2. Thus, inclusion of multiple independent assays markedly improved the accuracy of antibody tests in low seroprevalence communities and revealed differences in antibody kinetics depending on the viral antigen. In contrast to other reports, we conclude that immunity is durable for at least several months after SARS-CoV-2 infection.
- Ripperger, T. J., Uhrlaub, J. L., Watanabe, M., Wong, R., Castaneda, Y., Pizzato, H. A., Thompson, M. R., Bradshaw, C., Weinkauf, C. C., Bime, C., Erickson, H. L., Knox, K., Bixby, B., Parthasarathy, S., Chaudhary, S., Natt, B., Cristan, E., El Aini, T., Rischard, F., , Campion, J., et al. (2020). Orthogonal SARS-CoV-2 Serological Assays Enable Surveillance of Low-Prevalence Communities and Reveal Durable Humoral Immunity. Immunity, 53(5), 925-933.e4.More infoWe conducted a serological study to define correlates of immunity against SARS-CoV-2. Compared to those with mild coronavirus disease 2019 (COVID-19) cases, individuals with severe disease exhibited elevated virus-neutralizing titers and antibodies against the nucleocapsid (N) and the receptor binding domain (RBD) of the spike protein. Age and sex played lesser roles. All cases, including asymptomatic individuals, seroconverted by 2 weeks after PCR confirmation. Spike RBD and S2 and neutralizing antibodies remained detectable through 5-7 months after onset, whereas α-N titers diminished. Testing 5,882 members of the local community revealed only 1 sample with seroreactivity to both RBD and S2 that lacked neutralizing antibodies. This fidelity could not be achieved with either RBD or S2 alone. Thus, inclusion of multiple independent assays improved the accuracy of antibody tests in low-seroprevalence communities and revealed differences in antibody kinetics depending on the antigen. We conclude that neutralizing antibodies are stably produced for at least 5-7 months after SARS-CoV-2 infection.
- Altbach, M. I., Bilgin, A., Martin, D. R., Weinkauf, C. C., Fu, Z., Saranathan, M., Johnson, K., & Keerthivasan, M. B. (2019). An Efficient 3D Stack-of-Stars TSE Pulse Sequence for Simultaneous T2-weighted Imaging and T2 Mapping. Magnetic Resonance in Medicine, 82(1), 326-341.
- Keerthivasan, M. B., Saranathan, M., Johnson, K., Fu, Z., Weinkauf, C. C., Martin, D. R., Bilgin, A., & Altbach, M. I. (2019). An efficient 3D stack-of-stars turbo spin echo pulse sequence for simultaneous T2-weighted imaging and T2 mapping. Magnetic resonance in medicine, 82(1), 326-341.More infoTo design a pulse sequence for efficient 3D T2-weighted imaging and T2 mapping.
- Pandit, V., Lee, A., Zeeshan, M., Goshima, K., Tan, T. W., Jhajj, S., Trinidad, B., Weinkauf, C., & Zhou, W. (2019). Effect of frailty syndrome on the outcomes of patients with carotid stenosis. Journal of vascular surgery.More infoFrailty syndrome confers a greater risk of morbidity and mortality after operative interventions. The aim of the present study was to assess the effect of frailty on the outcomes after carotid interventions, including both carotid endarterectomy (CEA) and carotid artery stenting (CAS).
- Sabat, J., Bock, D., Hsu, C. H., Tan, T. W., Weinkauf, C., Trouard, T., Perez-Carrillo, G. G., & Zhou, W. (2019). Risk factors associated with microembolization after carotid intervention. Journal of vascular surgery.More infoMicroembolization after carotid artery stenting (CAS) and carotid endarterectomy (CEA) has been documented and may confer risk for neurocognitive impairment. Patients undergoing stenting are known to be at higher risk for microembolization. In this prospective cohort study, we compare the microembolization rates for patients undergoing CAS and CEA and perioperative characteristics that may be associated with microembolization.
- Sabat, J., Hsu, C. H., Samra, N., Chu, Q., Weinkauf, C., Goshima, K., Zhou, W., & Tan, T. W. (2019). Length of Stay and ICU Stay Are Increased With Repair of Traumatic Superior Mesenteric Vein Injury. The Journal of surgical research, 242, 94-99.More infoTraumatic superior mesenteric vein (SMV) injury is rare, and the ideal treatment is controversial. We compared the outcomes of ligation versus repair of SMV injury using the National Trauma Databank.
- Weinkauf, C., Mazhar, A., Vaishnav, K., Hamadani, A. A., Cuccia, D. J., & Armstrong, D. G. (2019). Near-instant noninvasive optical imaging of tissue perfusion for vascular assessment. Journal of vascular surgery.More infoNoninvasive vascular tests are critical for identifying patients who may benefit from surgical revascularization, but current tests have significant limitations in people with diabetes. This study aimed to evaluate the ability of spatial frequency domain imaging (SFDI), an optical imaging method capable of measuring tissue oxygen saturation (StO) and tissue hemoglobin, to assess lower extremity blood supply.
- Yanquez, F. J., Peterson, A., Weinkauf, C., Goshima, K. R., Zhou, W., Mohler, J., Ehsani, H., & Toosizadeh, N. (2019). Sensor-Based Upper-Extremity Frailty Assessment for the Vascular Surgery Risk Stratification. The Journal of surgical research.More infoAvailable methods for determining outcomes in vascular surgery patients are often subjective or not applicable in nonambulatory patients. The purpose of the present study was to assess the association between vascular surgery outcomes and a previously validated upper-extremity function (UEF) method, which incorporates wearable motion sensors for the physical frailty assessment.
- Moccetti, F., Weinkauf, C. C., Davidson, B. P., Belcik, J. T., Marinelli, E. R., Unger, E., & Lindner, J. R. (2018). Ultrasound Molecular Imaging of Atherosclerosis Using Small-Peptide Targeting Ligands Against Endothelial Markers of Inflammation and Oxidative Stress. Ultrasound in medicine & biology, 44(6), 1155-1163.More infoThe aim of this study was to evaluate a panel of endothelium-targeted microbubble (MB) ultrasound contrast agents bearing small peptide ligands as a human-ready approach for molecular imaging of markers of high-risk atherosclerotic plaque. Small peptide ligands with established affinity for human P-selectin, VCAM-1, LOX-1 and von Willebrand factor (VWF) were conjugated to the surface of lipid-stabilized MBs. Contrast-enhanced ultrasound (CEUS) molecular imaging of the thoracic aorta was performed in wild-type and gene-targeted mice with advanced atherosclerosis (DKO). Histology was performed on carotid endarterectomy samples from patients undergoing surgery for unstable atherosclerosis to assess target expression in humans. In DKO mice, CEUS signal for all four targeted MBs was significantly higher than that for control MBs, and was three to sevenfold higher than in wild-type mice, with the highest signal achieved for VCAM-1 and VWF. All molecular targets were present on the patient plaque surface but expression was greatest for VCAM-1 and VWF. We conclude that ultrasound contrast agents bearing small peptide ligands feasible for human use can be targeted against endothelial cell adhesion molecules for inflammatory cells and platelets for imaging advanced atherosclerotic disease.
- Trinidad, B., Weinkauf, C., & Hughes, J. (2018). Perigraft air mimicking infection on CT angiography following open abdominal aortic aneurysm repair. Radiology case reports, 13(2), 343-346.More infoAortic graft infection is a feared complication after open abdominal aortic aneurysm repair secondary to its high mortality. Perigraft air is a common finding after open aortic aneurysm repair; however, it is also associated with aortic graft infection. Delineating between graft infection and common postoperative finding is a challenge. This is further complicated by use of hemostatic agents such as Gelfoam, which is also documented to cause perigraft air. Correct diagnosis has crucial implications in management of potential aortic graft infection, which is a vascular emergency. We report a case of perigraft air in a patient status after open aortic aneurysm repair with associated clinical manifestations of infection in whom conservative management and surveillance was selected for treatment. We then discuss the timeline of perigraft air, potential causation, importance of history, and physical examination, and finally, we discuss how specific findings on computed tomography imaging for infection in other areas may be useful in aortic graft infection.
- Weinkauf, C. C., Concha-Moore, K., Lindner, J. R., Marinelli, E. R., Hadinger, K. P., Bhattacharjee, S., Berman, S. S., Goshima, K., Leon, L. R., Matsunaga, T. O., & Unger, E. (2018). Endothelial vascular cell adhesion molecule 1 is a marker for high-risk carotid plaques and target for ultrasound molecular imaging. Journal of vascular surgery, 68(6S), 105S-113S.More infoMolecular imaging of carotid plaque vulnerability to atheroembolic events is likely to lead to improvements in selection of patients for carotid endarterectomy (CEA). The aims of this study were to assess the relative value of endothelial inflammatory markers for this application and to develop molecular ultrasound contrast agents for their imaging.
- Weinkauf, C., George, E., & Zhou, W. (2017). Open versus endovascular aneurysm repair trial review. Surgery, 162(5), 974-978.More infoThe Open versus Endovascular Aneurysm Repair trial is the only randomized controlled trial that is funded by the federal government to evaluate the treatment outcomes of infrarenal abdominal aortic aneurysms. Since the initial publication, multiple post-hoc analyses have become available. This review summarizes these data, focusing on the primary outcome measures (ie, overall survival) and several key secondary outcomes including aneurysm-related death, age consideration, secondary procedures, and endoleaks. Cost-effectiveness of each treatment modality and the limitations of OVER trial also are discussed critically in this review.
- Umiker, B. R., Andersson, S., Fernandez, L., Korgaokar, P., Larbi, A., Pilichowska, M., Weinkauf, C. C., Wortis, H. H., Kearney, J. F., & Imanishi-Kari, T. (2014). Dosage of X-linked Toll-like receptor 8 determines gender differences in the development of systemic lupus erythematosus. European journal of immunology, 44(5), 1503-16.More infoSystemic lupus erythematosus (SLE) is an autoimmune disease with a high incidence in females and a complex phenotype. Using 564Igi mice, a model of SLE with knock-in genes encoding an autoreactive anti-RNA Ab, we investigated how expression of Toll-like receptors (TLRs) in B cells and neutrophils affects pathogenesis. We established that TLR signaling through MyD88 is necessary for disease. Autoantibody was produced in mice with single deletions of Tlr7, Tlr8, or Tlr9 or combined deletions of Tlr7 and Tlr9. Autoantibody was not produced in the combined absence of Tlr7 and Tlr8, indicating that TLR8 contributes to the break in tolerance. Furthermore, TLR8 was sufficient for the loss of B-cell tolerance, the production of class-switched autoantibody, heightened granulopoiesis, and increased production of type I IFN by neutrophils as well as glomerulonephritis and death. We show that dosage of X-linked Tlr8 plays a major role in the high incidence of disease in females. In addition, we show that the negative regulation of disease by TLR9 is exerted primarily on granulopoiesis and type I IFN production by neutrophils. Collectively, we suggest that individual TLRs play unique roles in the pathogenesis of systemic lupus erythematosus, suggesting new targets for treatment.
- Weinkauf, C., McPhillips, S., Krouse, R., & Levine, I. (2014). Autoimmune Gastrointestinal Paralysis: Failure of Conventional Treatment without Immunomodulation. Case reports in surgery, 2014, 180654.More infoThe treatment of the rare enteric nervous system (ENS) manifestations of paraneoplastic syndromes, which are most frequently associated with small cell lung cancer (SCLC), is poorly understood and described. Patients with neuroendocrine-derived tumors can develop B-cell reactivity towards the tumor with cross-reactivity for neurons located in the submucosal and myenteric ganglia of the ENS. The ensuing autoimmune neuritis causes aperistalsis and severe gastrointestinal (GI) dysfunction. Immune-directed therapy is not the standard of care but may be paramount for patient recovery. Our patient, a 63-year-old man with recent symptoms of esophageal dysmotility and newly diagnosed SCLC was hospitalized with nausea, emesis, and constipation. After an extensive work-up that included laparoscopy and celiotomy with bowel resection, we diagnosed what we refer to as Autoimmune Paraneoplastic Chronic Intestinal Pseudoobstruction (AP-CIPO). Unlike the few clinically similar reports, SCLC and AP-CIPO were diagnosed in our patient within weeks of each other, which presented the dilemma of treating the two processes simultaneously. In this report, we review the relevant literature and describe our patient's course. We believe standard chemotherapy is not effective treatment for AP-CIPO. Based on evidence discussed herein, we suggest initiating autoimmune-directed therapy before or simultaneous with cancer-directed therapy.
- Weinkauf, C., Salvador, R., & Pereiraperrin, M. (2011). Neurotrophin receptor TrkC is an entry receptor for Trypanosoma cruzi in neural, glial, and epithelial cells. Infection and immunity, 79(10), 4081-7.More infoTrypanosoma cruzi, the agent of Chagas' disease, infects a variety of mammalian cells in a process that includes multiple cycles of intracellular division and differentiation starting with host receptor recognition by a parasite ligand(s). Earlier work in our laboratory showed that the neurotrophin-3 (NT-3) receptor TrkC is activated by T. cruzi surface trans-sialidase, also known as parasite-derived neurotrophic factor (PDNF). However, it has remained unclear whether TrkC is used by T. cruzi to enter host cells. Here, we show that a neuronal cell line (PC12-NNR5) relatively resistant to T. cruzi became highly susceptible to infection when overexpressing human TrkC but not human TrkB. Furthermore, trkC transfection conferred an ∼3.0-fold intracellular growth advantage. Sialylation-deficient Chinese hamster ovarian (CHO) epithelial cell lines Lec1 and Lec2 also became much more permissive to T. cruzi after transfection with the trkC gene. Additionally, NT-3 specifically blocked T. cruzi infection of the TrkC-NNR5 transfectants and of naturally permissive TrkC-bearing Schwann cells and astrocytes, as did recombinant PDNF. Two specific inhibitors of Trk autophosphorylation (K252a and AG879) and inhibitors of Trk-induced MAPK/Erk (U0126) and Akt kinase (LY294002) signaling, but not an inhibitor of insulin-like growth factor 1 receptor, abrogated TrkC-mediated cell invasion. Antibody to TrkC blocked T. cruzi infection of the TrkC-NNR5 transfectants and of cells that naturally express TrkC. The TrkC antibody also significantly and specifically reduced cutaneous infection in a mouse model of acute Chagas' disease. TrkC is ubiquitously expressed in the peripheral and central nervous systems, and in nonneural cells infected by T. cruzi, including cardiac and gastrointestinal muscle cells. Thus, TrkC is implicated as a functional PDNF receptor in cell entry, independently of sialic acid recognition, mediating broad T. cruzi infection both in vitro and in vivo.
- Weinkauf, C., & Pereiraperrin, M. (2009). Trypanosoma cruzi promotes neuronal and glial cell survival through the neurotrophic receptor TrkC. Infection and immunity, 77(4), 1368-75.More infoTrypanosoma cruzi, the agent of Chagas' disease, promotes neuron survival through receptor tyrosine kinase TrkA and glycosylphosphatidylinositol-anchored glial cell-derived family ligand receptors (GFRalpha). However, these receptors are expressed by only a subset of neurons and at low levels or not at all in glial cells. Thus, T. cruzi might exploit an additional neurotrophic receptor(s) to maximize host-parasite equilibrium in the nervous system. We show here that T. cruzi binds TrkC, a neurotrophic receptor expressed by glial cells and many types of neurons, and that the binding is specifically inhibited by neurotrophin-3, the natural TrkC ligand. Coimmunoprecipitation and competition assays show that the trans-sialidase/parasite-derived neurotrophic factor (PDNF), previously identified as a TrkA ligand, mediates the T. cruzi-TrkC interaction. PDNF promotes TrkC-dependent mitogen-activated protein kinase signaling, neurite outgrowth, and survival of genetically engineered PC12 neuronal cells and glial Schwann cells in a TrkC-dependent manner. Thus, TrkC is a new neurotrophic receptor that T. cruzi engages to promote the survival of neuronal and glial cells. The results raise the possibility that T. cruzi recognition of TrkC underlies regenerative events in nervous tissues of patients with Chagas' disease.
- Theoharides, T. C., Weinkauf, C., & Conti, P. (2004). Brain cytokines and neuropsychiatric disorders. Journal of clinical psychopharmacology, 24(6), 577-81.
- Altbach, M. I., Weinkauf, C. C., Bilgin, A., Johnson, K., & Keerthivasan, M. B. (2019, May). Efficient T2 Mapping of the Carotid Artery using a 3D Stack-of-Stars Variable Flip Angle TSE Pulse Sequence. In 2019 Annual Meeting of the ISMRM, Montreal, QC, Canada.
- Weinkauf, C. C., Trouard, T. P., Chou, Y., Chen, N., Guzman Perez-Carrillo, G., Ryan, T. L., Altbach, M. I., Johnson, K., Bruck, D., Ugonna, C., McKinnon, A., Bernstein, A. S., & Lindley, M. (2019, Spring). Functional and Microstructural Changes in the Brain After Carotid Endarterectomy. In International Society for Magnetic Resonance in Medicine.
- Altbach, M. I., Bilgin, A., Martin, D. R., Weinkauf, C. C., Saranathan, M., Johnson, K., & Keerthivasan, M. B. (2018, June). An Optimized 3D Stack-of-Stars TSE Pulse Sequence for Simultaneous T2-weighted Imaging and T2 Mapping. In 2018 Meeting of the International Society for Magnetic Resonance in Medicine.
- Weinkauf, C. C., Trouard, T. P., Guzman Perez-Carrillo, G., Chou, Y., Chen, N., Ryan, L., Altbach, M. I., Johnson, K., Bruck, D., Ugonna, C., Bernstein, A., & Lindley, M. (2018, June). Impact of Carotid Endarterectomy on Functional Connectivity. In Joint International Society for Magnetic Resonance in Medicine & The European Society for Magnetic Resonance in Medicine and Biology (ISMRM-ESMRMB) Annual Meeting, 5562.
- Weinkauf, C. C., Weinkauf, C. C., Bilgin, A., Bilgin, A., Becker, J., Becker, J., Keerthivasan, M. B., Keerthivasan, M. B., Li, Z., Li, Z., Johnson, K., Johnson, K., Mandava, S., Mandava, S., Altbach, M. I., & Altbach, M. I. (2018, June). Rapid Carotid Artery T2 and T1 Mapping Using a Radial TSE and IR-FLASH Approach. In 2018 Meeting of the International Society for Magnetic Resonance in Medicine.
- Weinkauf, C. C., Bilgin, A., Becker, J., Keerthivasan, M. B., Li, Z., Johnson, K., Mandava, S., & Altbach, M. I. (2018, June). Rapid Carotid Artery T2 and T1 Mapping Using a Radial TSE and IR-FLASH Approach. In 2018 Meeting of the International Society for Magnetic Resonance in Medicine.
- Weinkauf, C. C. (2019, January 2019). Quantitative Evaluation of Cognition and Brain function in the Treatment of Extracranial Carotid Atherosclerosis. Banner Alzheimer’s Institute. Phoenix, AZ.
- Weinkauf, C. C. (2019, May 2019). Vertebrobasilar Insufficiency. Vascular Surgery Teaching Conference. College of Medicine: University of Arizona.
- Weinkauf, C. C. (2018, December). Introduction to Non-Cardiac Vascular Surgery Emergencies. Medicine Grand Rounds. College of Medicine: University of Arizona.