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Manuel Llano M.D., Ph.D.

Associate Professor

Biological Sciences Department

The University of Texas at El Paso PERSONAL DATA

• First Name: Manuel

• Last name: Llano

• Current Academic Rank: Associate Professor (Tenure)

• Department: Biological Sciences

• Office Address: Biosciences Building. Room 3144. 500 University Ave. El Paso, TX, 79968

• Phone: 915-747-6941

• Email: mllano@utep.edu

EDUCATION

• Ph. D., Universidad Autonoma de Madrid, Spain, 2000. Major: Molecular Biology

• Residency in Clinical Biochemistry, Universidad de La Habana, School of Medicine, Cuba, 1992.

• M.D., Universidad de La Habana, School of Medicine, Cuba, 1987.

POSITIONS

• 2000-2006: Research Associate, Molecular Medicine Department, Mayo Clinic. Rochester, MN.

• 2006-2012: Assistant Professor (tenure track), Biological Sciences Department, The University of

Texas at El Paso. El Paso, TX.

• 2012-present: Associate Professor (tenure), Biological Sciences Department, The University of Texas

at El Paso. El Paso, TX.

HONORS (last ten years)

• 2016: Outstanding Performance Award. Research and Sponsored Programs. The University of Texas

at El Paso

• 2012: Outstanding Performance Award. Research and Sponsored Programs. The University of Texas

at El Paso

• 2008: Outstanding Performance Award. Research and Sponsored Programs. The University of Texas

at El Paso

SUMMARY

I am a tenured Associated Professor with more than twenty years of expertise in basic research in virology and

immunology. I have taught over 3000 students in the last ten years, secured over 3.2 millions dollars in federal

research funds in the last decade, published 49 research articles, graduated six Ph.D. and three master in

science students, and served in a great variety of committees.

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RESEARCH

CONTRIBUTIONS TO SCIENCE

1. Fundamental role of HLA-E in the regulation of natural killer (NK) cells through the interaction with

CD94/NKG2 receptors. Functional regulation of NK cells occurs through the interaction of HLA class I

molecules in target cells and inhibitory or activatory receptors on the NK cell. These NK cell receptors are

grouped in two protein superfamilies: the immunoglobulin and the C type lectin superfamily. CD94/NKG2

receptors belong to the C type lectin superfamily. At the time that I started my Ph.D. training in the laboratory of

Miguel Lopez-Botet, Universidad Autonoma de Madrid, CD94/NKG2 receptors were considered to functionally

interact with a broad group of HLA class I molecules, including several members of the three classical HLA

class I molecules and also the non-classical class I molecule HLA-G. My research completely changed this

concept by the identification in 1998 of HLA-E as the sole CD94/NKG2 receptors ligand. In addition, these

findings identified a sensor mechanism of cellular class I expression, later demonstrated to be utilized by the

immune system and exploited by pathogenic viruses, based on the requirement of class I-derived peptides for

surface expression of HLA-E. During my tenure at Lopez-Botet lab I also demonstrated the functional relevance

of HLA-E-bound peptides in the interaction with CD94/NKG2, and identified a potential mechanism of

immunoevasion evolved by Cytomegalovirus based in the selective downregulation of the surface expression of

classical class I molecules, while preserving the expression of HLA-E.

1. Lee N.&; Llano M.&; Carretero M.; Ishitani A.; Navarro F.; Lopez-Botet M., Geraghty D. HLA-E is a major

ligand for the natural killer inhibitory receptor CD94/NKG2A. Proc. Natl. Acad. Sci. U.S.A. 95:5199-5204,

1998. & shared first autorship.

2. Llano M.; Lee N.; Navarro F.; Garcia P.; Albar J.P.; Geraghty D.E., Lopez-Botet M. HLA-E-bound peptides

influence recognition by inhibitory and triggering CD94/NKG2 receptors: preferential response to an HLA-G-

derived nonamer. Eur. J. Immunol. 28:2854-2863, 1998.

3. Garcia P., Llano M., de Heredia A.B., Willberg C.B., Caparros E., Aparicio P., Braud V.M., Lopez-Botet M.

Human T cell receptor-mediated recognition of HLA-E. Eur. J. Immunol. 32:936-944, 2002.

4. Llano M., Guma M., Ortega M., Angulo A., Lopez-Botet M. Differential effects of US2, US6 and US11

human cytomegalovirus proteins on HLA class Ia and HLA-E expression: impact on target susceptibility to

NK cell subsets. Eur J Immunol. 33:2744-2754, 2003.

2. Fundamental role of LEDGF/p75 in HIV-1 DNA integration and integration site selection. Between

2000 and 2006 I was an Associate Research at the laboratory Eric Poeschla, Mayo Clinic, leading a research

project devoted to the characterization of cellular cofactors of HIV-1 replication. I defined the fundamental role

of LEDGF/p75 in HIV-1 DNA integration and mapped functional domains in the protein identifying also the

molecular mechanism of action. In collaboration with the Bushman lab, University of Pennsylvania, we also

demonstrated the role of LEDGF/p75 in promoting integration within actively transcribed genes.

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1. Llano M., Vanegas M., Fregoso O., Saenz D., Chung S., Peretz M., Poeschla E.M. LEDGF/p75

determines cellular trafficking of diverse lentiviral but not murine oncoretroviral integrase proteins and is a

component of functional lentiviral preintegration complexes. J Virol. 78:9524-9537. 2004.

2. Ciuffi A., Llano M., Poeschla E.M., Marshall H., Hoffman C., Shinn P., Hannenhalli S., Ecker J., Bushman

F. A role for LEDGF/p75 in targeting HIV DNA integration. Nat. Med. 11:1287-1289, 2005.

3. Llano M., Saenz D.T., Meehan A., Wongthida P., Peretz M., Walker W.H., Teo W., and Poeschla E.M.. An

essential role of LEDGF/p75 in HIV integration. Science. 2006 314 (5798):461-4.

4. Llano M., Vanegas M., Hutchins N., Thompson D., Delgado S., Poeschla E.M. Identification and

characterization of the chromatin-binding domains of the HIV-1 integrase interactor LEDGF/p75. J. Mol.

Biol. 360:760-773, 2006.

3. Identification of LEDGF/p75-associated proteins implicated in HIV-1 replication. Research from my

laboratory at The University of Texas at El Paso has identified cellular proteins that interact with LEDGF/p75

and are implicated in HIV-1 replication. These proteins include PARP-1, a protein implicated in transcriptional

regulation and DNA repair, and SSRP1, a subunit of the transcriptional elongation factor FACT complex.

PARP-1 inhibition and/or deficiency significantly increase HIV-1 replication in immortal and resting memory

CD4+ T cells by enhancing provirus gene expression. Incomplete knockdown of SSRP1 partially reduces HIV-

1, but not Murine Leukemia Virus (MLV, a LEDGF/p75-independent retrovirus) infection in human CD4+ T cell

line SupT1. SSRP1 facilitates the expression of HIV-1 LTR-driven viral genes in an specific manner.

1. Gutierrez DA, Valdes L, Serguera C, Llano M. Poly (ADP-ribose) polymerase-1 silences retroviruses

independently of viral DNA integration or heterochromatin formation. J Gen Virol. 2016 Mar 30. [Epub

ahead of print]

2. Bueno MT, Reyes D, Valdes L, Saheba A, Urias E, Mendoza C, Fregoso OI, Llano M. Poly (ADP-ribose)

Polymerase-1 Promotes Transcriptional Repression of Integrated Retroviruses. J Virol. Mar; 87(5):2496-

507, 2013.

3. Lopez AP, Kugelman JR, Garcia-Rivera J, Urias E, Salinas SA, Fernandez-Zapico ME, Llano M. The

Structure-Specific Recognition Protein 1 Associates with Lens Epithelium-Derived Growth Factor Proteins

and Modulates HIV-1 Replication. J. Mol. Biol. 2016 Jul 17; 428(14):2814-31. doi:

10.1016/j.jmb.2016.05.013. Epub 2016 May 21. PMID: 27216501

4. Identification of novel HIV-1 maturation inhibitors. HIV-1 is released from infected cells as an immature,

non-infectious virion that then proceeds through maturation before gaining full infectivity. We have developed a

group of novel fullerene-derivatives that potently (IC50 0.3 μM) block HIV-1 infection at the maturation step.

These maturation inhibitors severely impair replication of HIV-1 resistant to multiple clinically used protease

inhibitors as well as to experimental maturation inhibitors. We hold two provisional US patents on these

maturation inhibitors.

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1. Characterization of new cationic [70]fullerene derivatives as potent HIV-1 maturation inhibitors". Castro, E.

Martinez, Z.S.; Seong, CS; Cabrera-Espinoza, A.; Ruiz, M.; Hernandez, A.; Valdez, F.; Llano, M*.;

Echegoyen, L. Journal of Medicinal Chemistry (jm-2016-00994h.R1, in press). *Shared senior authorship.

2. Martinez ZS, Castro E, Seong CS, Cerón MR, Echegoyen L, Llano M. Fullerene Derivatives Strongly

Inhibit HIV-1 Replication by Affecting Virus Maturation without Impairing Protease Activity. Antimicrob

Agents Chemother. 2016 Jul 18. pii: AAC.00341-16. PMID: 27431232

ONGOING RESEARCH PROJECTS My laboratory is interested in developing novel strategies to treat viral infections. We focus on two families of

viruses: HIV and mosquito-borne flaviviruses.

HIV Anti-retroviral drugs are very effective in controlling HIV-1 replication leading to prevention of AIDS

development and HIV-1 transmission. Similarly, some of these drugs are efficient in prophylaxis of infection of

at high risk individuals. Added to this scenario not clear evidences exist that a vaccine against HIV-1 will be

developed in the near future. Therefore anti-HIV-1 chemotherapy is an effective manner of controlling HIV-1

infection in the absence of an effective vaccine. The main problems with this therapeutic strategy are the

significant side effects that some of these drugs have, the viral resistance developed even when the drugs are

used in combination, and the incapacity of these drugs to eradicate the HIV latent reservoir, hence the

infection. Our laboratory is committed to the development of novel anti-HIV-1 strategies to solve some of these

important limitations by identifying novel therapeutic targets among cellular factors or viral processes.

Cellular Factors as anti-HIV therapeutic targets Currently, we are interested in host factors implicated in HIV-1 DNA integration or gene expression. Integration

is essential for HIV replication, and viral gene expression is central in HIV-1 latency that is the main barrier to

HIV infection eradication.

LEDGF/p75 is essential for HIV-1 integration Rationale: Integrase inhibitors have proven their clinical effectiveness, suggesting that other drugs able to

interfere with the viral DNA integration process will have a similar impact on HIV infection. I demonstrated that

LEDGF/p75 is a cellular factor essential for efficient HIV DNA integration. This cellular protein directly binds to

integrase promoting viral DNA integration. As a result, HIV replication is greatly impaired in cells lacking

LEDGF/p75 or expressing LEDGF/p75 mutants that inhibit the formation of the LEDGF/p75-integrase complex,

or in cells treated with compounds that bind to integrase blocking the LEDGF/p75 interaction. An important

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disadvantage of these integrase-binding compounds is due to the low genetic barrier of viral proteins, viral

resistance emerges. To solve this limitation, we plan to identify compounds blocking integrase-LEDGF/p75

interaction by binding to LEDGF/p75. LEDGF/p75 has been demonstrated to be redundant in the developed

mice and in cultured cells. Therefore, significant toxicity of these LEDGF/p75-binding compounds is unlikely.

Status: We have developed a cell-based high-throughput screening system for inhibitors of the LEDGF/p75-

Integrase interaction. We are now in the processes of acquiring a compound library to begin the screening.

Cellular Factors regulating HIV-1 gene expression Structure Specific Recognition Protein 1 (SSRP1) favors HIV-1 replication by enhancing viral promoter-

driven gene expression

Rationale: We have recently discovered that the host protein SSRP1 regulates HIV-1 gene expression at the

viral promoter level. LEDGF/p75 interacts with SSRP1, potentially facilitating its recruitment to the HIV-1

provirus.

Status: We are currently investigating the mechanism of action of SSRP1 in HIV-1 gene expression by

mapping the SSRP1 protein regions implicated in HIV-1 promoter regulation.

Poly (ADP-Ribose) Polymerase 1 (PARP-1) antagonizes HIV-1 replication by regulating HIV-1 gene

expression

Rationale: We have discovered that PARP-1 antagonizes HIV-1 replication. Human CD4 T cells lacking

PARP-1 expression or treated with a PARP-1 inhibitor are two logs more permissive to HIV-1 replication than

control cells. The mechanism involves enhanced viral promoter-driven HIV-1 gene expression in the absence

of functional PARP-1. Importantly, inhibition of PARP-1 also enhances HIV-1 replication in primary human CD4

T cells implicated in HIV latency, suggesting a role of this protein in latent infection.

Status: We are now investigating the mechanism of action of PARP-1 by evaluating the hypothesis that

PARP-1 affects HIV Env-CD4/Co-receptor signaling during entry, modulating in this manner the transcriptional

status of the target cell and therefore of the viral promoter.

Discovery of novel anti-HIV maturation inhibitors Rationale: HIV is produced by infected cells as an immature viral particle. Virion-associated HIV protease

triggers HIV maturation through a very well coordinated process of limited proteolysis of the structural poly-

proteins Gag and Gag/Pol. This essential process can be pharmacologically impaired by inhibiting the catalytic

activity of protease (protease inhibitors) or by altering the ability of the viral poly-proteins to serve as protease

substrates or to ensemble into highly organized structures (maturation inhibitors). Protease inhibitors

effectively block viral replication in patients and are a fundamental part of the current anti-HIV therapy. Due to

the complexity of the maturation process, protease inhibitors exhibit the higher genetic barrier to the

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development of escape mutations among all the clinically used anti-HIV drugs. No maturation inhibitors are in

clinical use yet and their development is currently an area of intense research.

Status: We have recently developed novel HIV-1 maturation inhibitors that are able to block infection by

viruses that escape all the clinically used protease inhibitors and the experimental maturation inhibitors

developed. We hold a patent on these compounds. We are currently determining the mechanism of action of

these compounds by mapping their molecular target.

Mosquito-borne flaviviruses (West Nile, Dengue, Zika viruses) Schlafen 11 negatively affects the replication of HIV and Mosquito-borne flaviviruses. Rationale: Despite the relevance of these viral infections for human health, no vaccines have been approved

for commercial use in humans against any of these viruses, nor have specific treatments been developed yet.

Therefore, the identification of relevant anti-viral targets is a pressing need.

Efficient protein translation is essential for viral replication in general but perhaps more important for HIV-1

whose structural genes contain a high proportion of AT-rich codons and for positive-sense single-stranded

RNA viruses whose replication is strictly dependent of the translation of the incoming viral genome, typically,

one per cell. Therefore, cellular factors controlling translation efficiency could be important regulators of the

replication of these viruses.

tRNA abundance is the limiting factor of efficient protein translation. The size and composition of the cellular

tRNA pool is determined by the rate of tRNA degration rather than its synthesis, since these molecules are

extremely stable. Therefore, we propose that cellular factors implicated in tRNA degradation could have

important antiviral effects on positive-sense single-stranded RNA and AT-rich viruses, such as Mosquito-borne

flaviviruses and HIV, respectively.

Based on this hypothesis we discovered that schlafen 11, an interferon-induced protein that regulates tRNA

abundance, antagonizes West Nile and Dengue viruses replication. This protein was also reported to impair

HIV-1 replication. We have demonstrated that the anti-viral effects of schlafen 11 share a similar mechanism of

action that involves tRNA degradation.

Status: We are currently investigating the implication of schlafen 11 in the replication of other positive-sense

single-stranded RNA viruses including Zika virus, and deciphering the viral antagonism mechanism developed

by West Nile Virus against this restriction factor. In addition, we are exploring the role of other cellular proteins

that regulate tRNA abundance in the replication of positive-sense single-stranded RNA viruses. Our findings

will be relevant for the development of anti-viral drugs against positive-sense single-stranded RNA viruses of

medical and bioterrorism relevance.

RESEARCH SUPPORT

ONGOING RESEARCH SUPPORT

SC1GM115240- Llano (PI)

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NIH-NIAID “Role of PARP-1 in HIV-1 latent infection” ($ 1,400,000.00)

Funding agent: NIH-NIAID

Goal: To determine the role of PARP-1 in HIV-1 latency and replication.

Role: PI. (02/01/2016 - 01/31/2020)

COMPLETED RESEARCH SUPPORT

NIH-funded grants

1. SC1AI098238- Llano (PI)

“Regulation of the HIV cofactor activity of LEDGF/p75 by interacting proteins” ($ 1,430,895.00)

Funding agent: NIH- NIAID

Goal: To determine the role of LEDGF/p75-interacting proteins in HIV-1 replication.

Role: PI. (07/01/2011 – 09/30/2015)

2. SC2GM082301-Llano (PI)

"Molecular Mechanism of HIV-1 DNA integration.," ($ 322,440.00, plus $ 84,844.00 supplement).

Funding agent: NIH-NIGMS

Goal: To determine the mechanism of LEDGF/p75 in HIV-1 integration.

Role: PI. (03/12/2008 – 02/28/2011)

3. NIH R01- Kan-Mitchell (PI)

“Mapping novel subdominal B*5701 epitopes in conserved regions of the HIV

Proteome”

Funding agent: NIH-NIAID

Goal: To identify and characterize novel HIV epitopes as vaccine candidates.

Role: Collaborator. (09/01/08 - 08/31/2012)

The University of Texas at El Paso intramural grants

1. Llano and Echegoyen (Co-PIs)

"Synthesis and Mechanistic Characterization of Novel Fullerene Derivatives as Anti-HIV Agents” ($

25,000.00)

Funding agent: The University of Texas at El Paso. College of Science. Multidisciplinary Pilot Project

Program.

Goal: To determine the anti-HIV-1 activity of novel fullerene derivatives and define their mechanism of

action.

Role: Co-PI (02/01/2014 – 02/01/2015)

2. Llano and Watts (Co-PIs)

"Role of innate immune mechanisms targeting enveloped and AT-rich genome viruses in West Nile Virus

infection" ($ 25,000.00).

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Funding agent: The University of Texas at El Paso. College of Science. Multidisciplinary Pilot Project

Goal: To define the role of tetherin and Schlafen 11 in the replication of West Nile Virus.

Role: Co-PI (02/01/2013 - 02/01/2014)

3. Llano (PI)

"Role of SUMOylation of LEDGF/p75 in HIV infection" ($5,000.00.)

Funding agent: The University of Texas at El Paso. University Research Institute Grant.

Goal: To evaluate the impact of SUMOylation in the role of LEDGF/p75 in HIV-1 infection.

Role: PI (01/01/2009 – 12/31/2009)

4. Llano (PI)

"Molecular mechanism of LEDGF/p75 in HIV integration ($4,895.00.)

Goal: To evaluate the chromatin tethering role of LEDGF/p75 in HIV-1 DNA integration.

Funding agent: The University of Texas at El Paso. University Research Institute Grant.

Role: PI (01/01/2006 – 12/31/2006)

PEER-REVIEWED PUBLICATIONS

Original papers (*Shared senior authorship; **Undergraduate and & Graduate Students in senior-authored

papers)

1. Defining Pharmacological Targets by Analysis of Virus–Host Protein Interactions. Llano, M and Pena-

Hernandez, M.A. Chapter 11. PROTEIN-PROTEIN INTERACTIONS IN HUMAN DISEASE, PART B,

edited by Rossen Donev. Elsevier Inc.

2. LEDGF/p75 Deficiency Increases Deletions at the HIV-1 cDNA Ends. Bueno MTD, Reyes D, Llano M.

Viruses. 2017, 9 (9). pii: E259. doi: 10.3390/v9090259

3. Modulation of chromatin structure by the FACT histone chaperone complex regulates HIV-1 integration.

Matysiak J, Lesbats P, Mauro E, Lapaillerie D, Dupuy JW, Lopez AP, Benleulmi MS, Calmels C,

Andreola ML, Ruff M, Llano M, Delelis O, Lavigne M, Parissi V. Retrovirology. 2017, 14 (1): 39. doi:

10.1186/s12977-017-0363-4.

4. Characterization of New Cationic N,N-Dimethyl [70] fulleropyrrolidinium Iodide Derivatives as Potent

HIV-1 Maturation Inhibitors. Castro, E&.; Martinez, Z. S&.; Seong, C.-S.; Cabrera-Espinoza, A&.; Ruiz,

M.; Hernandez Garcia&, A.; Valdez, F&.; Llano, M.*; Echegoyen, L. Journal of Medicinal Chemistry.

2016, 59, 10963.

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5. Martinez ZS&, Castro E&, Seong CS, Cerón MR, Echegoyen L, Llano M. Fullerene Derivatives

Strongly Inhibit HIV-1 Replication by Affecting Virus Maturation without Impairing Protease Activity.

Antimicrob Agents Chemother. 2016, 60 (10) 5731-41. PMID: 27431232

6. Lopez AP&, Kugelman JR&, Garcia-Rivera J&, Urias E**, Salinas SA**, Fernandez-Zapico ME, Llano

M. The Structure-Specific Recognition Protein 1 Associates with Lens Epithelium-Derived Growth

Factor Proteins and Modulates HIV-1 Replication. J. Mol. Biol. 2016 Jul 17; 428(14):2814-31. PMID:

27216501

7. Gutierrez DA&, Valdes L&, Serguera C, Llano M. Poly(ADP-ribose) polymerase-1 silences retroviruses

independently of viral DNA integration or heterochromatin formation. J. Gen. Virol. 2016 Jul;

97(7):1686-92. PMID: 27028089

8. Pope, W., Bowman, C., Russell, D., Hatfull, Llano M# et al. Whole genome comparison of a large

collection of mycobacteriophages reveals a continuum of phage genetic diversity. (ed., vol. 4). eLife

2015. http://elifesciences.org/content/4/e06416. #This is a report of a large set of data contributed by a

large number of authors from several academic institutions in USA. I am not the senior author, but a co-

author in this paper.

9. Leitz J, Reuschenbach, M, Lohrey C, Honegger A, Accardi R, Tommasino M, Llano M, von Knebel

Doeberitz M, Hoppe-Seyler K, and Hoppe-Seyler F Oncogenic Human Papillomaviruses Activate the

Tumor-Associated Lens Epithelial-Derived Growth Factor (LEDGF) Gene. PLOS Pathogens. 2014 Mar

6;10(3):e1003957.

10. Bueno MT&, Reyes D&, Valdes L, Saheba A**, Urias E**, Mendoza C**, Fregoso OI, Llano M. Poly

(ADP-ribose) Polymerase-1 Promotes Transcriptional Repression of Integrated Retroviruses. J Virol.

2013. Mar; 87(5):2496-507

11. Astiazaran P**, Bueno MT&, Morales E&, Kugelman JR&, Garcia-Rivera J&, Llano M. HIV-1 integrase

modulates the interaction of the HIV-1 cellular cofactor LEDGF/p75 with chromatin. Retrovirology. 2011

Apr 21;8:27

12. Bueno TDM&, Garcia-Rivera J&, Kugelman JR&, Morales E& and Llano M. SUMOylation of lens

epithelium-derived growth factor/p75 negatively affects its transcriptional activity on the heat shock

protein 27 promoter. J. Mol. Biol. 2010 Apr 8

13. Llano M, Morrison J, Poeschla EM. Virological and Cellular Roles of the Transcriptional Coactivator

LEDGF/p75. Curr Top Microbiol Immunol. 339:125-46. 2010

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14. Garcia-Rivera J&, Bueno MT&, Morales E&, Kugelman JR&, Rodriguez DF&, Llano M. Implication of

Serine Residues 271, 273 and 275 in the HIV-1 Cofactor Activity of LEDGF/p75. J Virol. 2010

Jan;84(2):740-52.

15. Meehan AM, Saenz DT, Morrison JH, Garcia-Rivera J, Peretz M, Llano M, Poeschla EM. LEDGF/p75

proteins with alternative chromatin tethers are functional HIV-1 cofactors. PLoS Pathog. 2009

Jul;5(7):e1000522. Epub 2009 Jul 17

16. Miest T, Saenz D, Meehan A, Llano M, Poeschla EM. Intensive RNAi with lentiviral vectors in

mammalian cells. Methods. 2009 Apr;47(4):298-303.

17. Llano, M, Gaznick N, Poeschla EM. Rapid, controlled and intensive lentiviral vector-based RNAi.

Methods Mol Biol. 2009;485:257-70.

18. Marshall HM, Ronen K, Berry C, Llano M, Sutherland H, Saenz D, Bickmore W, Poeschla EM,

Bushman F. Lentiviral infectivity and integration targeting. PLoS ONE 2(12):e1340 2007

19. Llano M., Saenz D.T., Meehan A., Wongthida P., Peretz M., Walker W.H., Teo W., and Poeschla E.M..

An essential role of LEDGF/p75 in HIV integration. Science. 2006 314 (5798):461-4.

20. Llano M., Vanegas M., Hutchins N., Thompson D., Delgado S., Poeschla E.M. Identification and

characterization of the chromatin-binding domains of the HIV-1 integrase interactor LEDGF/p75. J.

Mol. Biol. 360:760-773, 2006.

21. Ciuffi A., Llano M., Poeschla E.M., Marshall H., Hoffman C., Shinn P., Hannenhalli S., Ecker J.,

Bushman F. A role for LEDGF/p75 in targeting HIV DNA integration. Nat. Med. 11:1287-1289, 2005.

22. Vanegas M., Llano M., Delgado S., Thompson D., Peretz M., Poeschla E.M. Identification of the

LEDGF/p75 HIV-1 integrase-interaction domain and NLS reveals NLS-independent chromatin

tethering. J. Cell. Sci. 118:1733-1743. 2005.

23. Llano M., Vanegas M., Fregoso O., Saenz D., Chung S., Peretz M., Poeschla E.M. LEDGF/p75

determines cellular trafficking of diverse lentiviral but not murine oncoretroviral integrase proteins and is

a component of functional lentiviral preintegration complexes. J Virol. 78:9524-9537. 2004.

24. Llano M., Delgado S., Vanegas M., Poeschla E.M. LEDGF/p75 prevents proteasomal degradation of

HIV-1 integrase. J. Biol. Chem. 279: 55570-55577, 2004.

25. Garcia P., De Heredia A.B., Bellon T., Carpio E., Llano M., Caparros E., Aparicio P., Lopez-Botet M.

Signaling via CD70, a member of the TNF family regulates T cell functions. J. Leukoc. Biol. 76:263-270,

2004.

26. Nguyen K.-L., Llano M., Akari H., Miyagi E., Poeschla E.M., Strebel K., Bour S. Codon optimization of

the HIV-1 vpu and vif genes stabilizes their messenger RNA and allows for highly efficient Rev-

independent expression. Virology 319:163-175, 2004.

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27. Llano M., Guma M., Ortega M., Angulo A., Lopez-Botet M. Differential effects of US2, US6 and US11

human cytomegalovirus proteins on HLA class Ia and HLA-E expression: impact on target susceptibility

to NK cell subsets. Eur J Immunol. 33:2744-2754, 2003.

28. Llano M., Kelly T., Vanegas M., Peretz M., Peterson T.E., Simari R.D., Poeschla E.M. Blockade of

human immunodeficiency virus type 1 expression by caveolin-1. J Virol. 76:9152-9164, 2002.

29. Garcia P., Llano M., de Heredia A.B., Willberg C.B., Caparros E., Aparicio P., Braud V.M., Lopez-Botet

M. Human T cell receptor-mediated recognition of HLA-E. Eur. J. Immunol. 32:936-944, 2002.

30. Matamoros N., Mila J., Llano M., Balas A., Vicario J.L., Pons J., Crespi C., Martinez N., Iglesias-

Alzueta J., Lopez-Botet M. Molecular studies and NK cell function of a new case of TAP2 homozygous

human deficiency. Clin. Exp. Immunol.125:274-282, 2001.

31. Sancho D., Nieto M., Llano M., Rodriguez-Fernandez J.L., Tejedor R., Avraham S., Cabanas C.,

Lopez-Botet M., Sanchez-Madrid F. The tyrosine kinase PYK-2/RAFTK regulates natural killer (NK)

cell cytotoxic response and is translocated and activated upon specific target cell recognition and

killing. J. Cell Biol. 149:1249-1262, 2000.

32. Carretero M., Llano M., Navarro F., Bellon T., Lopez-Botet M. Mitogen-activated protein kinase activity

is involved in effector functions triggered by the CD94/NKG2-C NK receptor specific for HLA-E. Eur J

Immunol. 30:2842-2848, 2000.

33. Bellon T.; Heredia A.B.; Llano M.; Minguela A.; Rodriguez A.; Lopez-Botet M., Aparicio P. Triggering

of effector functions on a CD8+ T cell clone upon the aggregation of an activatory CD94/kp39

heterodimer. J. Immunol. 162:3996-4002, 1999.

34. Navarro F.; Llano M.; Bellon T.; Colonna M.; Geraghty D.E., Lopez-Botet M. The ILT2 (LIR1) and

CD94/NKG2A NK cell receptors respectively recognize HLA-G1 and HLA-E molecules co-expressed on

target cells. Eur. J. Immunol. 29:277-283, 1999.

35. Llano M.; Lee N.; Navarro F.; Garcia P.; Albar J.P.; Geraghty D.E., Lopez-Botet M. HLA-E-bound

peptides influence recognition by inhibitory and triggering CD94/NKG2 receptors: preferential response

to an HLA-G-derived nonamer. Eur. J. Immunol. 28:2854-2863, 1998.

36. Carretero M.; Palmieri G.; Llano M.; Tullio V.; Santoni A.; Geraghty D.E., Lopez-Botet M. Specific

engagement of the CD94/NKG2A killer inhibitory receptor by the HLA-E class Ib molecule induces

SHP-1 phosphatase recruitment to tyrosine-phosphorylated NKG2A: evidence for receptor function in

heterologous transfectants. Eur. J. Immunol. 28:1280-1291, 1998.

37. Llano M; Lee N.; Carretero M.; Ishitani A.; Navarro F.; Lopez-Botet M., Geraghty D. HLA-E is a major

ligand for the natural killer inhibitory receptor CD94/NKG2A. Proc. Natl. Acad. Sci. U.S.A. 95:5199-

5204, 1998. Shared first author.

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38. Perez-Villar J.J.; Melero I.; Navarro F.; Carretero M.; Bellon T.; Llano M.; Colonna M.; Geraghty D.,

Lopez-Botet M. The CD94/NKG2A inhibitory receptor complex is involved in natural killer cell-mediated

recognition of cells expressing HLA-G1. J. Immunol. 158: 5736-5743, 1997.

39. Colonna M.; Navarro F.; Bellon T.; Llano M.; Garcia P.; Samaridis J.; Angman L.; Cella M., Lopez-

Botet M. A common inhibitory receptor for major histocompatibility complex class I molecules on

human lymphoid and myelomonocytic cells. J. Exp. Med. 186: 1809-1818, 1997.

40. Pérez-Villar JJ, Melero I, Navarro F, Carretero M, Bellón T, Llano M, Colonna M, Geraghty DE, López-

Botet M.The CD94/NKG2-A inhibitory receptor complex is involved in natural killer cell-mediated

recognition of cells expressing HLA-G1. J Immunol. 1997 Jun 15;158(12):5736-43.

41. Fernández de Cossío ME, Ohlin M, Llano M, Selander B, Cruz S, del Valle J, Borrebaeck CA. Human

monoclonal antibodies against an epitope on the class 5c outer membrane protein common to many

pathogenic strains of Neisseria meningitidis. J Infect Dis. 1992 Dec;166(6):1322-8.

42. Hardy E, Ohlin M, Llano M. Enhanced ELISA sensitivity using TCA for efficient coating of biologically

active lipopolysaccharides or lipid A to the solid phase. J Immunol Methods. 1994 Nov 10;176(1):111-6.

Review papers

1. Llano M, Morrison J, and Poeschla EM. Virological and Cellular Roles of the Transcriptional

Coactivator LEDGF/p75. Curr Top Microbiol Immunol. 2010;339:125-46.

2. Lopez-Botet M., Llano M., Ortega M. Human cytomegalovirus and natural killer-mediated surveillance

of HLA class I expression: a paradigm of host-pathogen adaptation. Immunol. Rev. 181:193-202, 2001

3. Lopez-Botet, M.; Bellon, T.; Llano, M; Navarro, F.; Garcia, P. and de Miguel, M. Paired inhibitory and

triggering NK cell receptors for HLA class I molecules. Hum. Immunol. 61:7-17, 2000.

4. Lopez-Botet, M.; Llano, M.; Navarro, F.; and Bellon, T. NK cell recognition of non-classical HLA class I

molecules. Semin. Immunol. 12:109-119, 2000.

5. Lopez-Botet, M.; Navarro, F.; Llano, M. and Garcia, P. NK cell mediated recognition of HLA class Ib

molecules: role of CD94/NKG2 receptors. J. Reproduct. Immunol. 43:167– 3, 1999.

6. Lopez-Botet, M.; Navarro, F. and Llano, M. How does NK cells sense the expression of HLA-G class

Ib molecules? Semin. Cancer Biol. 9:19-26, 1999.

7. López-Botet M, Carretero M, Bellón T, Pérez-Villar JJ, Llano M, Navarro F. The CD94/NKG2 C-type

lectin receptor complex. Curr Top Microbiol Immunol. 1998;230:41-52.

8. López-Botet M, Carretero M, Bellón T, Pérez-Villar JJ, Llano M, Navarro F. The CD94/NKG2C-type

lectin receptor complex in recognition of HLA class I molecules. Res Immunol. 1997 Mar-

Apr;148(3):155-9.

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9. López-Botet M, Pérez-Villar JJ, Carretero M, Rodríguez A, Melero I, Bellón T, Llano M, Navarro F.

Structure and function of the CD94 C-type lectin receptor complex involved in recognition of HLA class I

molecules. Immunol Rev. 1997 Feb;155:165-74.

10. López-Botet M, Carretero M, Pérez-Villar J, Bellón T, Llano M, Navarro F.The CD94/NKG2 C-type

lectin receptor complex: involvement in NK cell-mediated recognition of HLA class I molecules.

Immunol Res. 1997;16(2):175-85.

INVITED SPEAKER TALKS 1. Infectious Disease Symposium: HIV immunopathogenesis and Gene Therapy, "Cellular Factors

Implicated in HIV-1 replication," Texas Tech University, Paul L. Foster School of Medicine. El Paso, TX

(2013).

2. Loma Linda School of Medicine "Role of LEDGF/p75 in HIV infection" Loma Linda, CA (2010).

3. The University of Alabama at Birmingham. "Cellular cofactors of HIV infection". Birmingham, AL (2012).

4. SACNAS National Conference. “Role of Cellular Factors in HIV-1 replication" in San Antonio, TX (2013)

INTELLECTUAL PROPERTY 1. Provisional Patent Application: 1,3-Dipolar[70] Fulleropyrrolidinium Iodide Derivatives by Luis A.

Echegoyen, Manuel Llano, Edison A Castro Portillo and Zachary Martinez(UTEP0022USP1 / 2015-

023)

2. Provisional Patent Application: [1,3]-Thiazine-Fulleropyrrolo Derivatives of C60 and C70 as HIV

Inhibitor Agents by Luis A. Echegoyen, Danisha Rivera-Nazario, Manuel Llano, Edison A Castro Portillo

and Zachary Martinez (UTSE.P0171US.P1 / 2015-045)

3. Provisional Patent Application: Screening System for detecting Inhibitors of HIV Integrase-LEDGF/p75

Interaction by Manuel Llano and Elisa Morales.

PRESENTATIONS AT RESEARCH MEETINGS (Only International meetings in the last nine years are

included). **Undergraduate and & Graduate Students

1. Gutierrez, D. &, Reyes, D. &, Bueno, M. &, Llano, M., Retroviruses. Cold Spring Harbor Laboratory

Meeting., "A SUMOylation-deficient LEDGF/p75 mutant exhibits reduced HIV-1 cofactor activity".

(Poster). Cold Spring Harbor Laboratory, New York. (May 2012).

2. Llano, M., Bueno, M. &, Reyes, D. &, Saheba, A. **, Urias, E. **, Mendoza, C. **, Rodriguez, L. &,

Fregoso, O. I., Retroviruses. Cold Spring Harbor Laboratory Meeting., "Poly (ADP-ribose) Polymerase-

1 Promotes Transcriptional Repression of Integrated RetrovirusesJ Virol". (Poster). (Oral presentation).

Cold Spring Harbor Laboratory, New York. (May 2012).

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3. Garcia-Rivera JA&, Bueno MT&, Morales E&, Kugelman JR&, Rodriguez DF&, Llano M. Implication of

Serine Residues 271, 273 and 275 in the HIV-1 Cofactor Activity of LEDGF/p75. (Poster). 3rd

International Conference on Retroviral Integrase. MBL Woods Hole, Boston (Sept. 14-18. 2008)

4. Bueno MT&, Garcia-Rivera JA&, Morales E&, Kugelman JR&, Cortez J**, Rosas-Acosta G, Llano M.

SUMOylation of LEDGF/p75 influences the subnuclear localization of HIV-1 integrase. (Poster). 3rd

International Conference on Retroviral Integrase. MBL Woods Hole, Boston (Sept. 14-18. 2008)

5. Meehan AM, Saenz DT, Morrison JH, Garcia-Rivera JA&, Peretz M, Llano M, Poeschla EM.

LEDGF/p75 proteins with alternative chromatin tethers are functional HIV-1 cofactors. Retroviruses

meeting. (Oral presentation). Cold Spring Harbor Laboratory. (May 2007)

15

TEACHING AND MENTORING I have taught in the classroom and the laboratory over 3,200 students in a variety of courses including

laboratory- and classroom-based, lower and higher division undergraduate and graduate courses (Table 1).

Among these courses, I developed CBCH 4320 and BIOL 5344 that have been offered continuously for the last

five and six years, respectively. In addition, I co-directed a freshmen level research-driven course funded by

HHMI/SEA undergraduate program (BIOL 1107) for the last six years. Last year I developed a second

freshmen research-driven course funded by NIH to be taught in Fall 2017. A description of the courses in table

1 is available upon request.

I have also trained over 50 undergraduate students that have entered in Ph.D., M.D., and M.D./Ph.D. programs

in very competitive schools nation-wide. I have also graduated six Ph.D. and three Master in Science students.

Five of the Ph.D. secured post-doctoral positions in prestigious institutions and two of them are currently

principal investigators at military-funded laboratories in USA. All the M.S. graduated has secured jobs as

technician in research laboratories immediately after graduation and still hold them. Two are in academia and

one in a military-funded lab.

TEACHING PHYLOSOPHY

Professional life has many routes and alternatives. In many occasions our decision of taking a particular route

is not well informed. Useful career information is often contaminated with futile information, or even hidden in

unsuspected places. The experience in looking for the adequate information and the experience of your own

and colleagues’ mistakes is an important source of useful information necessary to success. Therefore, to

succeed it is not only necessary to work hard, but also to do it in the right direction. But which one is the right

direction? This dilemma is very commonly encountered in our professional life, “I have decided to succeed, I

am determined to work very hard, but where should I head out to reach my goals?” At this point what is needed

is a mentor. This is a more experienced person who will altruistically guide you through your professional life-

decisions, helping you to conduct your efforts in the right direction. A mentor has to be also a role model that

inspires others. Therefore, achievement of professional excellence in each of our duties is necessary to

become a mentor.

My teaching philosophy is fully permeated by my interest in being an effective mentor for my students. As a

teacher I guide my students to learn what will be important to build their professional future. My goal in the

classroom is that students understand, rather than memorize, the information necessary to build further

knowledge. In order to do this, I motivate them by transmitting the passion that I feel for the subject that I teach

and also I appeal to their curiosity by using real life examples and logical analysis during the lectures.

In addition, I teach the students the philosophy of “you can do it” .This motivation helps them in the classroom

to acquire knowledge, but more importantly, helps them in their future professional and personal lives to

overcome obstacles. To effectively imprint in my students this philosophy, I constantly challenge them at the

lecture with reasoning questions that promote them to think and realize that they can come with good ideas to

solve real life problems. At these exercises I always insist “come on you can do it, think of how this can be

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solved”. Another tool I use to cultivate this philosophy in my students is to invite to the classroom guest

speakers. These professionally successful individuals serve as role models for my students, inspiring in them

self confidence.

A further important point in my teaching philosophy is that my role as a teacher does not end in the classroom

and it is not just limited to spreading knowledge in microbiology. Students from the course, from the laboratory

and in general from the Department seek advices from me to solve strategic problems in their professional life

and this greatly satisfies me. I have found that just investing a little of extra-time it has a big impact in the

academic progresses of students.

Table 1. Teaching summary. Period collected Fall 2006-Spring 2017 (3,208 students). Course types are

Teaching laboratory (TL), Lecture (L), Seminar (S), Team Taught course (TT), Research-Driven Lab (RL), and

mentoring (M). The maximum grade for the student’s course evaluations is 5. The numbers of semester

used to calculate the mean+/-SD of the student’s course evaluations are indicated in parentheses.

Course Course Name Total Enrollment

Course Type

Semesters taught

Level Student’s course

evaluation

BIOL 1103 Introductory Biology Lab

43 TL 2 Undergrad N/A

BIOL 5344 Molecular Pathogenesis

51 L + S 5 Doctoral 4.8+/-.17 (4)

CBCH 4310 Techniques in Molecular

Biochemistry

72 L + S, TT

2 Undergrad N/A

CBCH 4320 Advanced Topics in Molecular

Biochemistry

204 L + S, TT

6 Undergrad 4.3+/- 0.5 (6)

MICR 2141 General Microbiology Lab

93 TL 4 Undergrad N/A

MICR 2330 Microorganisms and disease

73 L 2 Undergrad 4.95+/- 0.07 (2)

MICR 2340 General Microbiology 829 L 9 Undergrad 4.58+/- 0.3 (7)

MICR 2440 General Microbiology 1,592 L + TL 17 Undergrad 4.6+/- 0.28 (17)

BIOL 1107 Topics in Study of Life

124 RL 7 Undergrad 4.92+/- 0.07 (3)

BIOL 4398

Special Problems 63 RL 22 Undergrad N/A

BIOL 5302 Research in Biological Sciences

21 RL 11 Doctoral N/A

BIOL 5398 Thesis 11 M 7 Doctoral N/A

BIOL 6X90 X=1-6

Independent Research

11 M 46 Doctoral N/A

BIOL 6399 Dissertation 11 M 9 Doctoral N/A

RSRC 4033 Undergraduate Research

10 RL 4 Undergrad N/A

FACULTY DEVELOPMENT COURSE (attended) Workshop, "Creative Active Learning Experiences," STEM Research-Teaching Integration Program. The

University of Texas at El Paso. (December 8, 2012).

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SERVICE AND LEADERSHIP

I have served as chair or member of different committees at the Departmental, College, and University levels

at The University of Texas at El Paso (UTEP) as well as at Texas Tech University Health Sciences Center. A

detailed description of dates, committees and roles is available upon request. These committees have been

responsible for organizing regional and national research symposiums (member, three committees), recruiting

faculty to UTEP (one committee chair, member in two committees), dictating University and Departmental

policies (members of the Institutional Review Board, of the Faculty Senate, and the Department Advisory

Committee), organizing Ph.D. programs (Director Graduate Student Seminar, member of the Pathobiology and

of the Cellular and Molecular Biochemistry Ph.D. Programs), or granting awards (Chair of the Departmental

Award Committee, and member of the University Undergraduate Scholarship Committee). I have also been the

faculty mentor of an Assistant Professor at the Department in the last two years.

As an expert in cellular cofactors of HIV replication, I have served for the last two years four times as reviewer

for NIH in the AIDS Molecular and Cellular Biology Study Section, and special emphasis panels Targeting

Persistent HIV Reservoirs and Basic Research on HIV Persistence. I have also served as a reviewer for grant

applications from the American Foundation for AIDS Research (AmFAR, USA), the K University Leuven

(Belgium), the Research Foundation-Flanders (Belgium), and the Israel Science Foundation.

I have also served as a reviewer for Microbiology textbooks from W.W. Norton & Company, and for articles

submitted to several research journals including PLOS Pathogens, J. Virology, Retrovirology, PLOS One,

Virology, Oncotarget, Future Virology, and Future Medicine.

In addition to be or have been Chair of the Dissertation Defense Committee of my eleven graduate students, I

am serving or have served as member of the Dissertation Defense Committee of twelve graduate students (8

Ph.D., 4 M.S.) in the Departments of Biological Sciences (10) and Chemistry (1) of UTEP, and in the

Dissertation Defense Committee of a Ph.D. students in the Pasteur Institute (France).

SERVICE PHYLOSOPHY I consider service a unique opportunity to contribute to society. I focus my service on mentoring students and

faculty. I make strategic recommendations to guide them toward their long term goals. I consider these

recommendations essential since many students are poorly informed about these matters until very late in their

college studies. At this late point, students frequently have limited chances to improve their extracurricular

activities and competitiveness. I also consider very important contributing to the community with my

professional expertise. In addition, service is always a learning opportunity to develop leadership and

organizational skills.

The following is a selection of the committees that I have served in the last decade: PROFESSIONAL SERVICE

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• Ad Hoc reviewer for NIH in the AIDS Molecular and Cellular Biology Study Section, and special

emphasis panels Targeting Persistent HIV Resevoirs and Basic Research on HIV Persistence (2015-

present).

• Ad Hoc reviewer for Journal of Virology, PLOS Pathogens, Retrovirology, Virology, PLOS One,

Oncotarget , Journal Future HIV Therapy, and Future Medicine (2007 - present)

• Ad hoc reviewer for Microbiology: An evolving Science. Slonczewski J.L. and Foster J.W. Editors W.W.

Norton & Company (2008 and 2013)

• Ad hoc reviewer for grants applications to the Israel Science Foundation (2013)

• Ad hoc reviewer for Postdoctoral Fellowship Research Foundation - Flanders (Belgium, 2009 and

2012)

• Ad hoc reviewer for grants applications to the K University Leuven (Belgium, 2010)

• Ad hoc reviewer for grants - The Foundation for AIDS Research (AmFAR, USA, 2009)

• Committee Member for 3rd Annual Research Colloquium, Texas Tech University Health Sciences

Center (2009)

DEPARTMENTAL SERVICE

• Chair Award Committee (2016-present)

• Faculty mentor for Anita Quintana, Ph.D, Assistant Professor (2015-present)

• Director Graduate Student Seminar (2010-present)

• Member of the Advisory Committee (2012-2016)

• Member of the Graduate School Selection Committee (2012-2014)

• Member for Doctor of Philosophy (Ph.D.) in Cellular and Molecular Biochemistry committee (2010-

present)

• Member for Cancer Biologist Search Committee (2012-2013)

COLLEGE SERVICE

• Chair for Geneticist Search Committee (2013-2014)

• Member of the organizing committee for the Symposium on Infectious Diseases and Health Disparity in

a Changing World (2010-2011 and 2016-present)

UNIVERSITY SERVICE

• Member of the Undergraduate Scholarship Committee (2010-2012)

• Member of the Faculty Senate (2010-2013)

• Member of the Institutional Review Board (2008-2013)