Carlos obtained his B.S. in Industrial Biotechnology from the University of Puerto Rico at Mayaguez. He received his PhD from the University of Colorado at Boulder working with Dr. Leslie Leinwand on myosin myopathies. His dissertation focused on analyzing the effects on myosin's cross-bridge cycle from mutations associated to Hypertrophic (HCM) and Dilated (DCM) cardiomyopathies. For his postdoc he will focus on disease mechanisms that can influence severity.

Stanford Advisors

All Publications

  • Generation of two induced pluripotent stem cell lines from patients suffering from pulmonary hypertension. Stem cell research Chen, G., Orozco, L., Parmisano, S., Jahng, J. W., Vera, C. D., Zhuge, Y., Wu, J. C., Obal, D. 2023; 72: 103218


    Idiopathic pulmonary arterial hypertension (IPAH) is a rare disease, with an estimated 500-1000 new cases diagnosed every year. A portion of these cases may be caused by mutations in the BMPR2 gene, suggesting a possible genetic component in the development of the disease. Here, we report two human induced pluripotent stem cell (iPSC) lines generated from IPAH patients. Both cell lines provide valuable insight into the molecular and cellular mechanisms of IPAH and can be used to further understand the disease.

    View details for DOI 10.1016/j.scr.2023.103218

    View details for PubMedID 37804546

  • Disparities in cardio-oncology: Implication of angiogenesis, inflammation, and chemotherapy. Life sciences Vera, C. D., Lopez, A. R., Ewaneewane, A. S., Lewis, K., Parmisano, S., Mondejar-Parreno, G., Upadhyaya, C., Mullen, M. 2023; 332: 122106


    Cancers and cardiovascular diseases are the top two causes of death in the United States. Over the past decades, novel therapies have slowed the cancer mortality rate, yet cardiac failures have risen due to the toxicity of cancer treatments. The mechanisms behind this relationship are poorly understood and it is crucial that we properly treat patients at risk of developing cardiac failure in response to cancer treatments. Currently, we rely on early-stage biomarkers of inflammation and angiogenesis to detect cardiotoxicity before it becomes irreversible. Identification of such biomarkers allows healthcare professionals to decrease the adverse effects of cancer therapies. Angiogenesis and inflammation have a systemic influence on the heart and vasculature following cancer therapy. In the field of cardio-oncology, there has been a recent emphasis on gender and racial disparities in cardiotoxicity and the impact of these disparities on disease outcomes, but there is a scarcity of data on how cardiotoxicity varies across diverse populations. Here, we will discuss how current markers of angiogenesis and inflammation induced by cancer therapy are related to disparities in cardiovascular health.

    View details for DOI 10.1016/j.lfs.2023.122106

    View details for PubMedID 37730108

  • Modulating fast skeletal muscle contraction protects skeletal muscle in animal models of Duchenne muscular dystrophy JOURNAL OF CLINICAL INVESTIGATION Russell, A. J., DuVall, M., Barthel, B., Qian, Y., Peter, A. K., Newell-Stamper, B. L., Hunt, K., Lehman, S., Madden, M., Schlachter, S., Robertson, B., Van Deusen, A., Rodriguez, H. M., Vera, C., Su, Y., Claflin, D. R., V. Brooks, S., Nghiem, P., Rutledge, A., Juehne, T. I., Yu, J., Barton, E. R., Luo, Y. E., Patsalos, A., Nagy, L., Sweeney, H., Leinwand, L. A., Koch, K. 2023; 133 (10)


    Duchenne muscular dystrophy (DMD) is a lethal muscle disease caused by absence of the protein dystrophin, which acts as a structural link between the basal lamina and contractile machinery to stabilize muscle membranes in response to mechanical stress. In DMD, mechanical stress leads to exaggerated membrane injury and fiber breakdown, with fast fibers being the most susceptible to damage. A major contributor to this injury is muscle contraction, controlled by the motor protein myosin. However, how muscle contraction and fast muscle fiber damage contribute to the pathophysiology of DMD has not been well characterized. We explored the role of fast skeletal muscle contraction in DMD with a potentially novel, selective, orally active inhibitor of fast skeletal muscle myosin, EDG-5506. Surprisingly, even modest decreases of contraction (<15%) were sufficient to protect skeletal muscles in dystrophic mdx mice from stress injury. Longer-term treatment also decreased muscle fibrosis in key disease-implicated tissues. Importantly, therapeutic levels of myosin inhibition with EDG-5506 did not detrimentally affect strength or coordination. Finally, in dystrophic dogs, EDG-5506 reversibly reduced circulating muscle injury biomarkers and increased habitual activity. This unexpected biology may represent an important alternative treatment strategy for Duchenne and related myopathies.

    View details for DOI 10.1172/JCI153837

    View details for Web of Science ID 000996649500003

    View details for PubMedID 36995778

    View details for PubMedCentralID PMC10178848

  • Generation of two iPSC lines from long QT syndrome patients carrying SNTA1 variants. Stem cell research Jimenez-Tellez, N., Vera, C. D., Yildirim, Z., Vicente Guevara, J., Zhang, T., Wu, J. C. 2022; 66: 103003


    Long QT syndrome (LQTS) is an inherited cardiovascular disorder characterized by electrical conduction abnormalities leading to arrhythmia, fainting, seizures, and an increased risk of sudden death. There are over 15 genes involved in causing LQTS, including SNTA1. Here we generated two human-induced pluripotent stem cell (iPSC) lines from two LQT patients carrying a missense mutation in SNTA1 (c.1088A>C). Both lines showed normal morphological properties, expressed pluripotency markers, showed a normal karyotype profile, and had the ability to differentiate into the three germ layers, making them a valuable tool to model LQTS to investigate the pathological mechanisms related to this SNTA1 variant.

    View details for DOI 10.1016/j.scr.2022.103003

    View details for PubMedID 36528013

  • Generation of human induced pluripotent stem cell lines carrying heterozygous PLN mutation from dilated cardiomyopathy patients. Stem cell research Caudal, A., Mondejar-Parreno, G., Vera, C. D., Williams, D. R., Shenoy, S. P., Liang, D., Wu, J. C. 2022; 63: 102855


    Familial dilated cardiomyopathy (DCM) is among the most prevalent forms of inherited heart disease. Here, two human-induced pluripotent stem cell (iPSC) lines were generated from peripheral blood mononuclear cells (PBMCs) from DCM patients carrying different mutations in the phospholamban encoding-gene (PLN). Both iPSC lines exhibited normal morphology, karyotype, pluripotency marker expression, and differentiation into the three germ layers. These patient-specific iPSC lines serve as valuable in vitro models for DCM pathology caused by PLN mutations.

    View details for DOI 10.1016/j.scr.2022.102855

    View details for PubMedID 35853412

  • Generation of two induced pluripotent stem cell lines carrying the phospholamban R14del mutation for modeling ARVD/C. Stem cell research Vera, C. D., Manhas, A., Shenoy, S. P., Wheeler, M. T., Sallam, K., Wu, J. C. 2022; 63: 102834


    The phospholamban (PLN) R14del mutation is associated with arrhythmogenic right ventricular dysplasia (ARVD/C). ARVD/C is a cardiac disease characterized by arrhythmias and structural abnormalities in the right ventricle. Because PLN is a regulator of calcium release, this mutation can have deleterious effects on tissue integrity and contraction. This mutation is a trinucleotide (AGA) deletion that leads to an arginine deletion at position 14 of the PLN structure. Here we show two lines carrying this mutation with typical iPSC morphology, pluripotency, karyotype, ability to differentiate into the three germ layers in vitro, and readily availability for studying pathological mechanisms or ARVD/C.

    View details for DOI 10.1016/j.scr.2022.102834

    View details for PubMedID 35700631

  • Intersectionality and genetic ancestry: New methods to solve old problems. EBioMedicine Vera, C. D., Mullen, M., Minhas, N., Wu, J. C. 2022; 80: 104049

    View details for DOI 10.1016/j.ebiom.2022.104049

    View details for PubMedID 35561454

  • Generation of two iPSC lines from hypertrophic cardiomyopathy patients carrying MYBPC3 and PRKAG2 variants. Stem cell research Manhas, A., Jahng, J. W., Vera, C. D., Shenoy, S. P., Knowles, J. W., Wu, J. C. 2022; 61: 102774


    Hypertrophic cardiomyopathy (HCM) is an inherited cardiac disorder characterized by a thick left ventricular wall and an increased risk of arrhythmias, heart failure, and sudden cardiac death. The MYBPC3 and PRAKG2 are known causal genes for HCM. Here we generated two human-induced pluripotent stem cell lines from two HCM patients carrying two heterozygous mutations in MYBPC3 (c.459delC) and PRKAG2 (c.1703C > T). Both iPSC lines expressed pluripotent markers, had a normal karyotype, and were able to differentiate into three germ layers, making them potentially valuable tools for modeling HCM in vitro and investigating the pathological mechanisms related to these two variants.

    View details for DOI 10.1016/j.scr.2022.102774

    View details for PubMedID 35413566

  • Treating Duchenne Muscular Dystrophy: The Promise of Stem Cells, Artificial Intelligence, and Multi-Omics. Frontiers in cardiovascular medicine Vera, C. D., Zhang, A., Pang, P. D., Wu, J. C. 2022; 9: 851491


    Muscular dystrophies are chronic and debilitating disorders caused by progressive muscle wasting. Duchenne muscular dystrophy (DMD) is the most common type. DMD is a well-characterized genetic disorder caused by the absence of dystrophin. Although some therapies exist to treat the symptoms and there are ongoing efforts to correct the underlying molecular defect, patients with muscular dystrophies would greatly benefit from new therapies that target the specific pathways contributing directly to the muscle disorders. Three new advances are poised to change the landscape of therapies for muscular dystrophies such as DMD. First, the advent of human induced pluripotent stem cells (iPSCs) allows researchers to design effective treatment strategies that make up for the gaps missed by conventional "one size fits all" strategies. By characterizing tissue alterations with single-cell resolution and having molecular profiles for therapeutic treatments for a variety of cell types, clinical researchers can design multi-pronged interventions to not just delay degenerative processes, but regenerate healthy tissues. Second, artificial intelligence (AI) will play a significant role in developing future therapies by allowing the aggregation and synthesis of large and disparate datasets to help reveal underlying molecular mechanisms. Third, disease models using a high volume of multi-omics data gathered from diverse sources carry valuable information about converging and diverging pathways. Using these new tools, the results of previous and emerging studies will catalyze precision medicine-based drug development that can tackle devastating disorders such as DMD.

    View details for DOI 10.3389/fcvm.2022.851491

    View details for PubMedID 35360042

  • Identification of sequence changes in myosin II that adjust muscle contraction velocity PLOS BIOLOGY Johnson, C. A., McGreig, J. E., Jeanfavre, S. T., Walklate, J., Vera, C. D., Farre, M., Mulvihill, D. P., Baines, A. J., Ridout, M., Leinwand, L. A., Wass, M. N., Geeves, M. A. 2021; 19 (6): e3001248


    The speed of muscle contraction is related to body size; muscles in larger species contract at slower rates. Since contraction speed is a property of the myosin isoform expressed in a muscle, we investigated how sequence changes in a range of muscle myosin II isoforms enable this slower rate of muscle contraction. We considered 798 sequences from 13 mammalian myosin II isoforms to identify any adaptation to increasing body mass. We identified a correlation between body mass and sequence divergence for the motor domain of the 4 major adult myosin II isoforms (β/Type I, IIa, IIb, and IIx), suggesting that these isoforms have adapted to increasing body mass. In contrast, the non-muscle and developmental isoforms show no correlation of sequence divergence with body mass. Analysis of the motor domain sequence of β-myosin (predominant myosin in Type I/slow and cardiac muscle) from 67 mammals from 2 distinct clades identifies 16 sites, out of 800, associated with body mass (padj < 0.05) but not with the clade (padj > 0.05). Both clades change the same small set of amino acids, in the same order from small to large mammals, suggesting a limited number of ways in which contraction velocity can be successfully manipulated. To test this relationship, the 9 sites that differ between human and rat were mutated in the human β-myosin to match the rat sequence. Biochemical analysis revealed that the rat-human β-myosin chimera functioned like the native rat myosin with a 2-fold increase in both motility and in the rate of ADP release from the actin-myosin crossbridge (the step that limits contraction velocity). Thus, these sequence changes indicate adaptation of β-myosin as species mass increased to enable a reduced contraction velocity and heart rate.

    View details for DOI 10.1371/journal.pbio.3001248

    View details for Web of Science ID 000664238600002

    View details for PubMedID 34111116

    View details for PubMedCentralID PMC8191873

  • The ATPase cycle of human muscle myosin II isoforms: Adaptation of a single mechanochemical cycle for different physiological roles JOURNAL OF BIOLOGICAL CHEMISTRY Johnson, C. A., Walklate, J., Svicevic, M., Mijailovich, S. M., Vera, C., Karabina, A., Leinwand, L. A., Geeves, M. A. 2019; 294 (39): 14267-14278


    Striated muscle myosins are encoded by a large gene family in all mammals, including humans. These isoforms define several of the key characteristics of the different striated muscle fiber types, including maximum shortening velocity. We have previously used recombinant isoforms of the motor domains of seven different human myosin isoforms to define the actin·myosin cross-bridge cycle in solution. Here, we present data on an eighth isoform, the perinatal, which has not previously been characterized. The perinatal is distinct from the embryonic isoform, appearing to have features in common with the adult fast-muscle isoforms, including weak affinity of ADP for actin·myosin and fast ADP release. We go on to use a recently developed modeling approach, MUSICO, to explore how well the experimentally defined cross-bridge cycles for each isoform in solution can predict the characteristics of muscle fiber contraction, including duty ratio, shortening velocity, ATP economy, and load dependence of these parameters. The work shows that the parameters of the cross-bridge cycle predict many of the major characteristics of each muscle fiber type and raises the question of what sequence changes are responsible for these characteristics.

    View details for DOI 10.1074/jbc.RA119.009825

    View details for Web of Science ID 000499248200010

    View details for PubMedID 31387944

    View details for PubMedCentralID PMC6768639

  • Myosin motor domains carrying mutations implicated in early or late onset hypertrophic cardiomyopathy have similar properties. The Journal of biological chemistry Vera, C. D., Johnson, C. A., Walklate, J. n., Adhikari, A. n., Svicevic, M. n., Mijailovich, S. M., Combs, A. C., Langer, S. J., Ruppel, K. M., Spudich, J. A., Geeves, M. A., Leinwand, L. A. 2019


    Hypertrophic cardiomyopathy (HCM) is a common genetic disorder characterized by left ventricular hypertrophy and cardiac hyper-contractility. Mutations in the β cardiac myosin heavy chain gene (β-MyHC) are a major cause of HCM, but the specific mechanistic changes to myosin function that lead to this disease remain incompletely understood. Predicting the severity of any β-MyHC mutation is hindered by a lack of detailed examinations at the molecular level. Moreover, since HCM can take ≥20 years to develop, the severity of the mutations must be somewhat subtle. We hypothesized that mutations that result in early onset disease would have more severe changes in function than do later onset mutations. Here, we performed steady-state and transient kinetic analyses of myosins carrying one of seven missense mutations in the motor domain. Of these seven, four were previously identified in early onset cardiomyopathy screens. We used the parameters derived from these analyses to model the ATP driven cross-bridge cycle. Contrary to our hypothesis, the results indicated no clear differences between early and late onset HCM mutations. Despite the lack of distinction between early and late onset HCM, the predicted occupancy of the force-holding actin.myosin.ADP complex at [Actin] = 3 Kapp along with the closely related duty ratio (DR; the fraction of myosin in strongly attached force-holding states) and the measured ATPases all changed in parallel (in both sign and degree of change) compared to wild type (WT) values. Six of the seven HCM mutations were clearly distinct from a set of previously characterized DCM mutations.

    View details for DOI 10.1074/jbc.RA119.010563

    View details for PubMedID 31582565

  • Dilated cardiomyopathy myosin mutants have reduced force-generating capacity JOURNAL OF BIOLOGICAL CHEMISTRY Ujfalusi, Z., Vera, C. D., Mijailovich, S. M., Svicevic, M., Yu, E., Kawana, M., Ruppel, K. M., Spudich, J. A., Geeves, M. A., Leinwand, L. A. 2018; 293 (23): 9017–29


    Dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM) can cause arrhythmias, heart failure, and cardiac death. Here, we functionally characterized the motor domains of five DCM-causing mutations in human β-cardiac myosin. Kinetic analyses of the individual events in the ATPase cycle revealed that each mutation alters different steps in this cycle. For example, different mutations gave enhanced or reduced rate constants of ATP binding, ATP hydrolysis, or ADP release or exhibited altered ATP, ADP, or actin affinity. Local effects dominated, no common pattern accounted for the similar mutant phenotype, and there was no distinct set of changes that distinguished DCM mutations from previously analyzed HCM myosin mutations. That said, using our data to model the complete ATPase contraction cycle revealed additional critical insights. Four of the DCM mutations lowered the duty ratio (the ATPase cycle portion when myosin strongly binds actin) because of reduced occupancy of the force-holding A·M·D complex in the steady state. Under load, the A·M·D state is predicted to increase owing to a reduced rate constant for ADP release, and this effect was blunted for all five DCM mutations. We observed the opposite effects for two HCM mutations, namely R403Q and R453C. Moreover, the analysis predicted more economical use of ATP by the DCM mutants than by WT and the HCM mutants. Our findings indicate that DCM mutants have a deficit in force generation and force-holding capacity due to the reduced occupancy of the force-holding state.

    View details for PubMedID 29666183

    View details for PubMedCentralID PMC5995530

  • The Most Prevalent Freeman-Sheldon Syndrome Mutations in the Embryonic Myosin Motor Share Functional Defects JOURNAL OF BIOLOGICAL CHEMISTRY Walklate, J., Vera, C., Bloemink, M. J., Geeves, M. A., Leinwand, L. 2016; 291 (19): 10318-10331


    The embryonic myosin isoform is expressed during fetal development and rapidly down-regulated after birth. Freeman-Sheldon syndrome (FSS) is a disease associated with missense mutations in the motor domain of this myosin. It is the most severe form of distal arthrogryposis, leading to overcontraction of the hands, feet, and orofacial muscles and other joints of the body. Availability of human embryonic muscle tissue has been a limiting factor in investigating the properties of this isoform and its mutations. Using a recombinant expression system, we have studied homogeneous samples of human motors for the WT and three of the most common FSS mutants: R672H, R672C, and T178I. Our data suggest that the WT embryonic myosin motor is similar in contractile speed to the slow type I/β cardiac based on the rate constant for ADP release and ADP affinity for actin-myosin. All three FSS mutations show dramatic changes in kinetic properties, most notably the slowing of the apparent ATP hydrolysis step (reduced 5-9-fold), leading to a longer lived detached state and a slowed Vmax of the ATPase (2-35-fold), indicating a slower cycling time. These mutations therefore seriously disrupt myosin function.

    View details for DOI 10.1074/jbc.M115.707489

    View details for Web of Science ID 000375602800038

    View details for PubMedID 26945064

    View details for PubMedCentralID PMC4858979

  • The Hypertrophic Cardiomyopathy Myosin Mutation R453C Alters ATP Binding and Hydrolysis of Human Cardiac beta- Myosin* JOURNAL OF BIOLOGICAL CHEMISTRY Bloemink, M., Deacon, J., Langer, S., Vera, C., Combs, A., Leinwand, L., Geeves, M. A. 2014; 289 (8): 5158-5167


    The human hypertrophic cardiomyopathy mutation R453C results in one of the more severe forms of the myopathy. Arg-453 is found in a conserved surface loop of the upper 50-kDa domain of the myosin motor domain and lies between the nucleotide binding pocket and the actin binding site. It connects to the cardiomyopathy loop via a long α-helix, helix O, and to Switch-2 via the fifth strand of the central β-sheet. The mutation is, therefore, in a position to perturb a wide range of myosin molecular activities. We report here the first detailed biochemical kinetic analysis of the motor domain of the human β-cardiac myosin carrying the R453C mutation. A recent report of the same mutation (Sommese, R. F., Sung, J., Nag, S., Sutton, S., Deacon, J. C., Choe, E., Leinwand, L. A., Ruppel, K., and Spudich, J. A. (2013) Proc. Natl. Acad. Sci. U.S.A. 110, 12607-12612) found reduced ATPase and in vitro motility but increased force production using an optical trap. Surprisingly, our results show that the mutation alters few biochemical kinetic parameters significantly. The exceptions are the rate constants for ATP binding to the motor domain (reduced by 35%) and the ATP hydrolysis step/recovery stroke (slowed 3-fold), which could be the rate-limiting step for the ATPase cycle. Effects of the mutation on the recovery stroke are consistent with a perturbation of Switch-2 closure, which is required for the recovery stroke and the subsequent ATP hydrolysis.

    View details for DOI 10.1074/jbc.M113.511204

    View details for Web of Science ID 000331607900058

    View details for PubMedID 24344137

    View details for PubMedCentralID PMC3931073

  • Rapid Identification of Monospecific Monoclonal Antibodies Using a Human Proteome Microarray MOLECULAR & CELLULAR PROTEOMICS Jeong, J., Jiang, L., Albino, E., Marrero, J., Rho, H., Hu, J., Hu, S., Vera, C., Bayron-Poueymiroy, D., Rivera-Pacheco, Z., Ramos, L., Torres-Castro, C., Qian, J., Bonaventura, J., Boeke, J. D., Yap, W. Y., Pino, I., Eichinger, D. J., Zhu, H., Blackshaw, S. 2012; 11 (6): O111.016253


    To broaden the range of tools available for proteomic research, we generated a library of 16,368 unique full-length human ORFs that are expressible as N-terminal GST-His(6) fusion proteins. Following expression in yeast, these proteins were then individually purified and used to construct a human proteome microarray. To demonstrate the usefulness of this reagent, we developed a streamlined strategy for the production of monospecific monoclonal antibodies that used immunization with live human cells and microarray-based analysis of antibody specificity as its central components. We showed that microarray-based analysis of antibody specificity can be performed efficiently using a two-dimensional pooling strategy. We also demonstrated that our immunization and selection strategies result in a large fraction of monospecific monoclonal antibodies that are both immunoblot and immunoprecipitation grade. Our data indicate that the pipeline provides a robust platform for the generation of monoclonal antibodies of exceptional specificity.

    View details for DOI 10.1074/mcp.O111.016253

    View details for Web of Science ID 000306408500027

    View details for PubMedID 22307071

    View details for PubMedCentralID PMC3433917